Nucleocytoplasmic Shuttling of p53 Is Essential for MDM2-Mediated Cytoplasmic Degradation but Not Ubiquitination

Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from...

Full description

Saved in:
Bibliographic Details
Published inMolecular and Cellular Biology Vol. 23; no. 18; pp. 6396 - 6405
Main Authors O'Keefe, Kevin, Li, Huiping, Zhang, Yanping
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.09.2003
Taylor & Francis
Subjects
Active Transport, Cell Nucleus - physiology
Amino Acid Sequence
Amino Acids - chemistry
Cell Growth and Development
Cell Nucleus - metabolism
Cells, Cultured
Conserved Sequence
Cytoplasm - metabolism
Humans
Hydrophobic and Hydrophilic Interactions
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Nuclear Localization Signals
Nuclear Proteins
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-mdm2
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Ubiquitin - metabolism
Online AccessGet full text
ISSN0270-7306
1098-5549
1067-8824
1098-5549
DOI10.1128/MCB.23.18.6396-6405.2003

Cover

Abstract Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to MCB .asm.org, visit: MCB       
AbstractList As a shuttling protein, p53 is constantly transported through the nuclear pore complex. p53 nucleocytoplasmic transport is carried out by a bipartite nuclear localization signal (NLS) located at its C-terminal domain and two nuclear export signals (NES) located in its N- and C-terminal regions, respectively. The role of nucleocytoplasmic shuttling in p53 ubiquitination and degradation has been a subject of debate. Here we show that the two basic amino acid groups in the p53 bipartite NLS function collaboratively to import p53. Mutations disrupting individual amino acids in the NLS, although causing accumulation of p53 in the cytoplasm to various degrees, reduce but do not eliminate the NLS activity, and these mutants remain sensitive to MDM2 degradation. However, disrupting both parts of the bipartite NLS completely blocks p53 from entering the nucleus and causes p53 to become resistant to MDM2-mediated degradation. Similarly, mutations disrupting four conserved hydrophobic amino acids in the p53 C-terminal NES block p53 export and prohibit it from MDM2 degradation. We also show that colocalization of a nonshuttling p53 with MDM2 either in the nucleus or in the cytoplasm is sufficient for MDM2-induced p53 polyubiquitination but not degradation. Our data provide new insight into the mechanism and regulation of p53 nucleocytoplasmic shuttling and degradation.
Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to MCB .asm.org, visit: MCB       
As a shuttling protein, p53 is constantly transported through the nuclear pore complex. p53 nucleocytoplasmic transport is carried out by a bipartite nuclear localization signal (NLS) located at its C-terminal domain and two nuclear export signals (NES) located in its N- and C-terminal regions, respectively. The role of nucleocytoplasmic shuttling in p53 ubiquitination and degradation has been a subject of debate. Here we show that the two basic amino acid groups in the p53 bipartite NLS function collaboratively to import p53. Mutations disrupting individual amino acids in the NLS, although causing accumulation of p53 in the cytoplasm to various degrees, reduce but do not eliminate the NLS activity, and these mutants remain sensitive to MDM2 degradation. However, disrupting both parts of the bipartite NLS completely blocks p53 from entering the nucleus and causes p53 to become resistant to MDM2-mediated degradation. Similarly, mutations disrupting four conserved hydrophobic amino acids in the p53 C-terminal NES block p53 export and prohibit it from MDM2 degradation. We also show that colocalization of a nonshuttling p53 with MDM2 either in the nucleus or in the cytoplasm is sufficient for MDM2-induced p53 polyubiquitination but not degradation. Our data provide new insight into the mechanism and regulation of p53 nucleocytoplasmic shuttling and degradation.As a shuttling protein, p53 is constantly transported through the nuclear pore complex. p53 nucleocytoplasmic transport is carried out by a bipartite nuclear localization signal (NLS) located at its C-terminal domain and two nuclear export signals (NES) located in its N- and C-terminal regions, respectively. The role of nucleocytoplasmic shuttling in p53 ubiquitination and degradation has been a subject of debate. Here we show that the two basic amino acid groups in the p53 bipartite NLS function collaboratively to import p53. Mutations disrupting individual amino acids in the NLS, although causing accumulation of p53 in the cytoplasm to various degrees, reduce but do not eliminate the NLS activity, and these mutants remain sensitive to MDM2 degradation. However, disrupting both parts of the bipartite NLS completely blocks p53 from entering the nucleus and causes p53 to become resistant to MDM2-mediated degradation. Similarly, mutations disrupting four conserved hydrophobic amino acids in the p53 C-terminal NES block p53 export and prohibit it from MDM2 degradation. We also show that colocalization of a nonshuttling p53 with MDM2 either in the nucleus or in the cytoplasm is sufficient for MDM2-induced p53 polyubiquitination but not degradation. Our data provide new insight into the mechanism and regulation of p53 nucleocytoplasmic shuttling and degradation.
Author Huiping Li
Kevin O'Keefe
Yanping Zhang
AuthorAffiliation Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009
AuthorAffiliation_xml – name: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009
Author_xml – sequence: 1
  givenname: Kevin
  surname: O'Keefe
  fullname: O'Keefe, Kevin
  organization: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009
– sequence: 2
  givenname: Huiping
  surname: Li
  fullname: Li, Huiping
  organization: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009
– sequence: 3
  givenname: Yanping
  surname: Zhang
  fullname: Zhang, Yanping
  organization: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009
BackLink https://www.ncbi.nlm.nih.gov/pubmed/12944468$$D View this record in MEDLINE/PubMed
BookMark eNqNUk1vEzEUtFARTQN_AVkcuG3qj-yufQAJ0lIqNeUAPVter50Yee2t7SXKv2fTRLRE4uNgWX6eGb2Z987AiQ9eAwAxmmFM2Ply8XFG6AyzWUV5VVRzVM4IQvQZmGDEWVGWc34CJojUqKgpqk7BWUrfEUIVR_QFOMWEz-fzik1Afzsop4Pa5tA7mTqr4Nf1kLOzfgWDgX1J4XWClylpn6100IQIlxdLUix1a2XWLVw84V7oVZStzDZ42AwZ3oYM7xp7P9hs_UP5JXhupEv61eGegrtPl98Wn4ubL1fXiw83hSopzYVsGGdGlZi2NaVVTU3TalJK0nLMsSrrypi6MbunVIyWRCKpNDU14Q3GvKJTwPe6g-_ldiOdE320nYxbgZHYpSg61QhCBWZil6LYpSh2KY7cd3tuPzSdbtVoPcpHfpBW_P7j7Vqswg-BOa3HMwVvD_wY7gedsuhsUto56XUYkqhpObog1T-BmDGKCSEj8PXTjh6tHAY5At7vASqGlKI2Qtn8EPjYoHW_PI-b8yfP7EjgOK6_UBd7qvXjdnRyE6JrRZZbF6KJ0iubBP0PlTd7lbVdrTc2ajGu1NGM6E81q-jc
CitedBy_id crossref_primary_10_1016_j_celrep_2022_111177
crossref_primary_10_1016_j_semcancer_2024_05_001
crossref_primary_10_1186_1471_2121_11_74
crossref_primary_10_1016_j_lfs_2023_121477
crossref_primary_10_4161_19336918_2014_969998
crossref_primary_10_1016_j_biocel_2009_07_013
crossref_primary_10_1371_journal_pgen_1000240
crossref_primary_10_1074_jbc_M400946200
crossref_primary_10_1038_cddis_2014_438
crossref_primary_10_1042_BJ20050960
crossref_primary_10_1128_MCB_25_21_9392_9405_2005
crossref_primary_10_1590_S1984_29612016058
crossref_primary_10_7554_eLife_08401
crossref_primary_10_1016_j_bbcan_2005_08_008
crossref_primary_10_1095_biolreprod_108_070102
crossref_primary_10_1016_j_molmed_2009_09_005
crossref_primary_10_1021_cr400585q
crossref_primary_10_1038_sj_onc_1208897
crossref_primary_10_1074_jbc_M114_580209
crossref_primary_10_1038_srep06179
crossref_primary_10_3390_ijms25137465
crossref_primary_10_1083_jcb_201010051
crossref_primary_10_1101_gad_304071_117
crossref_primary_10_1158_1541_7786_MCR_06_0395
crossref_primary_10_1016_j_freeradbiomed_2005_04_028
crossref_primary_10_1126_science_1230835
crossref_primary_10_1021_mp300543t
crossref_primary_10_1016_j_devcel_2021_03_011
crossref_primary_10_1039_C9RA00808J
crossref_primary_10_1242_jcs_061010
crossref_primary_10_1002_mc_20151
crossref_primary_10_1158_0008_5472_CAN_04_2419
crossref_primary_10_1371_journal_pone_0008503
crossref_primary_10_1007_s10147_013_0639_1
crossref_primary_10_1016_j_colsurfb_2006_11_003
crossref_primary_10_1038_s41418_019_0293_x
crossref_primary_10_1111_j_1349_7006_2011_01899_x
crossref_primary_10_1074_jbc_M311123200
crossref_primary_10_1007_s13353_014_0239_4
crossref_primary_10_1111_acel_13003
crossref_primary_10_1038_sj_onc_1208785
crossref_primary_10_1186_1746_1596_5_72
crossref_primary_10_1093_carcin_bgp196
crossref_primary_10_18632_oncotarget_25944
crossref_primary_10_1016_j_ccr_2011_11_016
crossref_primary_10_1210_me_2006_0101
crossref_primary_10_1038_nature06128
crossref_primary_10_1074_jbc_M805696200
crossref_primary_10_3390_ijms17121997
crossref_primary_10_1158_1541_7786_MCR_06_0338
crossref_primary_10_3390_cancers13174284
crossref_primary_10_3390_ph17010113
crossref_primary_10_1128_MCB_24_19_8477_8486_2004
crossref_primary_10_1128_MCB_01307_06
crossref_primary_10_1042_BSR20090107
crossref_primary_10_1083_jcb_201309107
crossref_primary_10_1111_j_1600_0854_2009_00892_x
crossref_primary_10_1186_s12929_021_00753_3
crossref_primary_10_4291_wjgp_v14_i3_46
crossref_primary_10_1073_pnas_2321438121
crossref_primary_10_1038_s41418_017_0016_0
crossref_primary_10_1021_ja910688s
crossref_primary_10_1073_pnas_0501459102
crossref_primary_10_3109_10409230903401507
crossref_primary_10_1073_pnas_0804608105
crossref_primary_10_1074_jbc_M312712200
crossref_primary_10_1186_1752_0509_7_83
crossref_primary_10_1093_nar_gkr401
crossref_primary_10_1074_jbc_M109_081042
crossref_primary_10_1128_JVI_79_14_8773_8783_2005
crossref_primary_10_1007_s00018_022_04345_8
crossref_primary_10_1016_j_lfs_2007_08_029
crossref_primary_10_3390_cells8101248
crossref_primary_10_1016_j_stem_2013_07_018
crossref_primary_10_1186_s12860_021_00385_3
crossref_primary_10_1515_hsz_2018_0193
crossref_primary_10_1038_sj_onc_1209490
crossref_primary_10_1186_s12951_018_0395_5
crossref_primary_10_1016_j_drup_2003_10_004
crossref_primary_10_1007_s10565_015_9299_4
crossref_primary_10_1128_MCB_01830_05
crossref_primary_10_1093_carcin_bgs162
crossref_primary_10_1002_dvdy_656
crossref_primary_10_1016_j_celrep_2022_111920
crossref_primary_10_1128_MCB_01817_05
Cites_doi 10.1101/gad.12.19.2973
10.1016/0092-8674(92)90644-R
10.1128/MCB.22.17.6170-6182.2002
10.1073/pnas.86.23.9327
10.1016/S0955-0674(00)00216-7
10.1038/386779a0
10.1073/pnas.96.6.3077
10.1038/sj.onc.1203980
10.1038/sj.onc.1202951
10.1073/pnas.96.12.6937
10.1016/S0014-5793(97)01480-4
10.1016/S0092-8674(00)80416-X
10.1101/gad.7.7a.1126
10.1126/science.1058637
10.1128/MCB.20.21.8185-8197.2000
10.1038/nature737
10.1016/S0959-437X(99)00038-6
10.1101/gad.11.15.1974
10.1038/35042675
10.1002/j.1460-2075.1993.tb05678.x
10.1128/MCB.18.12.7288
10.1016/0092-8674(95)90435-2
10.1093/emboj/18.6.1660
10.1016/S1097-2765(00)80351-2
10.1093/emboj/17.2.554
10.1096/fj.01-0617fje
10.1038/sj.onc.1203012
10.1006/excr.2001.5314
10.1038/35023500
10.1006/excr.2000.4825
10.1093/emboj/18.1.22
10.1038/387299a0
10.1016/S0092-8674(00)81401-4
10.1038/387296a0
10.1016/S0092-8674(00)81400-2
10.1038/35023507
ContentType Journal Article
Copyright Copyright © 2003, American Society for Microbiology 2003
Copyright_xml – notice: Copyright © 2003, American Society for Microbiology 2003
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
8FD
FR3
P64
RC3
7X8
5PM
ADTOC
UNPAY
DOI 10.1128/MCB.23.18.6396-6405.2003
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Technology Research Database
Engineering Research Database
Biotechnology and BioEngineering Abstracts
Genetics Abstracts
MEDLINE - Academic
PubMed Central (Full Participant titles)
Unpaywall for CDI: Periodical Content
Unpaywall
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Genetics Abstracts
Engineering Research Database
Technology Research Database
Biotechnology and BioEngineering Abstracts
MEDLINE - Academic
DatabaseTitleList
Genetics Abstracts


MEDLINE
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 3
  dbid: UNPAY
  name: Unpaywall
  url: https://proxy.k.utb.cz/login?url=https://unpaywall.org/
  sourceTypes: Open Access Repository
DeliveryMethod fulltext_linktorsrc
Discipline Chemistry
Biology
EISSN 1098-5549
EndPage 6405
ExternalDocumentID oai:pubmedcentral.nih.gov:193719
PMC193719
12944468
10_1128_MCB_23_18_6396_6405_2003
12267586
mcb_23_18_6396
Genre Research Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S
Journal Article
GrantInformation_xml – fundername: NCI NIH HHS
  grantid: R01 CA100302
– fundername: NCI NIH HHS
  grantid: K01 CA087580
GroupedDBID ---
-DZ
-~X
.55
.GJ
0R~
123
18M
29M
2WC
39C
3O-
4.4
53G
5RE
5VS
9M8
ACGFO
ACKIV
ACNCT
ADBBV
ADIYS
AENEX
AEOZL
AFFNX
AGHSJ
AGVNZ
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
BTFSW
C1A
CS3
DIK
DU5
E3Z
EBS
EJD
F5P
GX1
H13
HH5
HYE
HZ~
IH2
KQ8
L7B
M4Z
MVM
N9A
O9-
OK1
P2P
RHF
RHI
RNS
RPM
RSF
TDBHL
TFL
TFW
TR2
UCJ
UDS
VQA
W8F
WH7
WHG
WOQ
X7M
Y6R
ZCA
ZGI
AAGFI
AAYXX
ABJNI
ADXHL
CITATION
TASJS
ABRLO
ABTAH
CGR
CUY
CVF
ECM
EIF
EMOBN
NPM
PKN
YIN
YYP
ZXP
ZY4
8FD
FR3
P64
RC3
7X8
5PM
ADTOC
UNPAY
ID FETCH-LOGICAL-c533t-ab898fc513d733673fbde25a2d9191c576ff7bf2d91ac8352a0ace3f729b11963
IEDL.DBID UNPAY
ISSN 0270-7306
1098-5549
1067-8824
IngestDate Tue Aug 19 23:51:48 EDT 2025
Thu Aug 21 13:57:57 EDT 2025
Wed Oct 01 15:00:31 EDT 2025
Fri Sep 05 06:46:46 EDT 2025
Wed Feb 19 02:02:46 EST 2025
Wed Oct 01 01:52:11 EDT 2025
Thu Apr 24 23:11:34 EDT 2025
Wed Dec 25 09:06:02 EST 2024
Wed May 18 15:25:58 EDT 2016
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 18
Language English
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c533t-ab898fc513d733673fbde25a2d9191c576ff7bf2d91ac8352a0ace3f729b11963
Notes ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
Corresponding author. Mailing address: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009. Phone: (713) 792-8969. Fax: (713) 792-8969. E-mail: ypzhang@mdanderson.org.
OpenAccessLink https://proxy.k.utb.cz/login?url=https://www.ncbi.nlm.nih.gov/pmc/articles/193719
PMID 12944468
PQID 18831222
PQPubID 23462
PageCount 10
ParticipantIDs pubmed_primary_12944468
informaworld_taylorfrancis_310_1128_MCB_23_18_6396_6405_2003
highwire_asm_mcb_23_18_6396
proquest_miscellaneous_73591926
crossref_primary_10_1128_MCB_23_18_6396_6405_2003
pubmedcentral_primary_oai_pubmedcentral_nih_gov_193719
crossref_citationtrail_10_1128_MCB_23_18_6396_6405_2003
proquest_miscellaneous_18831222
unpaywall_primary_10_1128_mcb_23_18_6396_6405_2003
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2003-09-01
PublicationDateYYYYMMDD 2003-09-01
PublicationDate_xml – month: 09
  year: 2003
  text: 2003-09-01
  day: 01
PublicationDecade 2000
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Molecular and Cellular Biology
PublicationTitleAlternate Mol Cell Biol
PublicationYear 2003
Publisher American Society for Microbiology
Taylor & Francis
Publisher_xml – name: American Society for Microbiology
– name: Taylor & Francis
References Kubbutat M. H. G. (R15) 1997; 387
Shieh S.-Y. (R25) 1997; 91
Haupt Y. (R11) 1997; 387
Wen W. (R32) 1995; 82
Ashcroft M. (R1) 1999; 18
Shirangi T. R. (R26) 2002; 16
Blattner C. (R4) 2002; 22
Zhang Y. (R38) 2001; 292
Zhang Y. (R39) 1998; 92
Nigg E. A. (R20) 1997; 386
Momand J. (R19) 1992; 69
Sherr C. J. (R24) 2000; 10
Giaccia A. J. (R10) 1998; 12
Liang S.-H. (R17) 2001; 274
Li M. (R16) 2002; 416
Tao W. (R28) 1999; 96
Honda R. (R14) 1999; 18
Geyer R. K. (R9) 2000; 2
Freedman D. A. (R7) 1998; 18
Zhang Y. (R36) 2001; 12
Roth J. (R22) 1998; 17
Henderson B. (R12) 2001; 256
Wu X. (R33) 1993; 7
Boyd S. D. (R5) 2000; 2
Benditt J. O. (R3) 1989; 86
Meek D. W. (R18) 1999; 18
Ryan K. M. (R23) 2001; 13
Thut C. J. (R30) 1997; 11
Zhang Y. (R37) 1999; 3
Tao W. (R29) 1999; 96
Barak Y. (R2) 1993; 12
Furukawa M. (R8) 2000; 20
Vogelstein B. (R31) 2000; 408
Honda R. (R13) 1997; 420
Pomerantz J. (R21) 1998; 92
Stommel J. M. (R27) 1999; 18
Xirodimas D. P. (R34) 2001; 270
Yu Z. K. (R35) 2000; 19
Chen J. (R6) 1995; 1
References_xml – volume: 12
  start-page: 2973
  year: 1998
  ident: R10
  publication-title: Genes Dev.
  doi: 10.1101/gad.12.19.2973
– volume: 69
  start-page: 1237
  year: 1992
  ident: R19
  publication-title: Cell
  doi: 10.1016/0092-8674(92)90644-R
– volume: 22
  start-page: 6170
  year: 2002
  ident: R4
  publication-title: Mol. Cell. Biol.
  doi: 10.1128/MCB.22.17.6170-6182.2002
– volume: 86
  start-page: 9327
  year: 1989
  ident: R3
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.86.23.9327
– volume: 13
  start-page: 332
  year: 2001
  ident: R23
  publication-title: Curr. Opin. Cell Biol.
  doi: 10.1016/S0955-0674(00)00216-7
– volume: 386
  start-page: 779
  year: 1997
  ident: R20
  publication-title: Nature
  doi: 10.1038/386779a0
– volume: 96
  start-page: 3077
  year: 1999
  ident: R28
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.96.6.3077
– volume: 19
  start-page: 5892
  year: 2000
  ident: R35
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1203980
– volume: 18
  start-page: 7666
  year: 1999
  ident: R18
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1202951
– volume: 96
  start-page: 6937
  year: 1999
  ident: R29
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.96.12.6937
– volume: 420
  start-page: 25
  year: 1997
  ident: R13
  publication-title: FEBS Lett.
  doi: 10.1016/S0014-5793(97)01480-4
– volume: 91
  start-page: 325
  year: 1997
  ident: R25
  publication-title: Cell
  doi: 10.1016/S0092-8674(00)80416-X
– volume: 7
  start-page: 1126
  year: 1993
  ident: R33
  publication-title: Genes Dev.
  doi: 10.1101/gad.7.7a.1126
– volume: 292
  start-page: 1910
  year: 2001
  ident: R38
  publication-title: Science
  doi: 10.1126/science.1058637
– volume: 20
  start-page: 8185
  year: 2000
  ident: R8
  publication-title: Mol. Cell. Biol.
  doi: 10.1128/MCB.20.21.8185-8197.2000
– volume: 416
  start-page: 648
  year: 2002
  ident: R16
  publication-title: Nature
  doi: 10.1038/nature737
– volume: 10
  start-page: 94
  year: 2000
  ident: R24
  publication-title: Curr. Opin. Genet. Dev.
  doi: 10.1016/S0959-437X(99)00038-6
– volume: 274
  start-page: 32699
  year: 2001
  ident: R17
  publication-title: J. Biochem.
– volume: 11
  start-page: 1974
  year: 1997
  ident: R30
  publication-title: Genes Dev.
  doi: 10.1101/gad.11.15.1974
– volume: 408
  start-page: 307
  year: 2000
  ident: R31
  publication-title: Nature
  doi: 10.1038/35042675
– volume: 12
  start-page: 461
  year: 1993
  ident: R2
  publication-title: EMBO J.
  doi: 10.1002/j.1460-2075.1993.tb05678.x
– volume: 18
  start-page: 7288
  year: 1998
  ident: R7
  publication-title: Mol. Cell. Biol.
  doi: 10.1128/MCB.18.12.7288
– volume: 82
  start-page: 463
  year: 1995
  ident: R32
  publication-title: Cell
  doi: 10.1016/0092-8674(95)90435-2
– volume: 18
  start-page: 1660
  year: 1999
  ident: R27
  publication-title: EMBO J.
  doi: 10.1093/emboj/18.6.1660
– volume: 3
  start-page: 579
  year: 1999
  ident: R37
  publication-title: Mol. Cell
  doi: 10.1016/S1097-2765(00)80351-2
– volume: 17
  start-page: 554
  year: 1998
  ident: R22
  publication-title: EMBO J.
  doi: 10.1093/emboj/17.2.554
– volume: 16
  start-page: 420
  year: 2002
  ident: R26
  publication-title: FASEB J.
  doi: 10.1096/fj.01-0617fje
– volume: 18
  start-page: 7637
  year: 1999
  ident: R1
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1203012
– volume: 270
  start-page: 66
  year: 2001
  ident: R34
  publication-title: Exp. Cell Res.
  doi: 10.1006/excr.2001.5314
– volume: 2
  start-page: 563
  year: 2000
  ident: R5
  publication-title: Nat. Cell Biol.
  doi: 10.1038/35023500
– volume: 256
  start-page: 213
  year: 2001
  ident: R12
  publication-title: Exp. Cell Res.
  doi: 10.1006/excr.2000.4825
– volume: 18
  start-page: 22
  year: 1999
  ident: R14
  publication-title: EMBO J.
  doi: 10.1093/emboj/18.1.22
– volume: 387
  start-page: 299
  year: 1997
  ident: R15
  publication-title: Nature
  doi: 10.1038/387299a0
– volume: 12
  start-page: 175
  year: 2001
  ident: R36
  publication-title: Cell Growth Differ.
– volume: 1
  start-page: 142
  year: 1995
  ident: R6
  publication-title: Med.
– volume: 92
  start-page: 725
  year: 1998
  ident: R39
  publication-title: Cell
  doi: 10.1016/S0092-8674(00)81401-4
– volume: 387
  start-page: 296
  year: 1997
  ident: R11
  publication-title: Nature
  doi: 10.1038/387296a0
– volume: 92
  start-page: 713
  year: 1998
  ident: R21
  publication-title: Cell
  doi: 10.1016/S0092-8674(00)81400-2
– volume: 2
  start-page: 569
  year: 2000
  ident: R9
  publication-title: Nat. Cell Biol.
  doi: 10.1038/35023507
SSID ssj0006903
Score 2.1266685
Snippet Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley...
As a shuttling protein, p53 is constantly transported through the nuclear pore complex. p53 nucleocytoplasmic transport is carried out by a bipartite nuclear...
SourceID unpaywall
pubmedcentral
proquest
pubmed
crossref
informaworld
highwire
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 6396
SubjectTerms Active Transport, Cell Nucleus - physiology
Amino Acid Sequence
Amino Acids - chemistry
Cell Growth and Development
Cell Nucleus - metabolism
Cells, Cultured
Conserved Sequence
Cytoplasm - metabolism
Humans
Hydrophobic and Hydrophilic Interactions
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Nuclear Localization Signals
Nuclear Proteins
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-mdm2
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Ubiquitin - metabolism
Title Nucleocytoplasmic Shuttling of p53 Is Essential for MDM2-Mediated Cytoplasmic Degradation but Not Ubiquitination
URI http://mcb.asm.org/content/23/18/6396.abstract
https://www.tandfonline.com/doi/abs/10.1128/MCB.23.18.6396-6405.2003
https://www.ncbi.nlm.nih.gov/pubmed/12944468
https://www.proquest.com/docview/18831222
https://www.proquest.com/docview/73591926
https://pubmed.ncbi.nlm.nih.gov/PMC193719
https://www.ncbi.nlm.nih.gov/pmc/articles/193719
UnpaywallVersion submittedVersion
Volume 23
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVFSB
  databaseName: Free Full-Text Journals in Chemistry
  customDbUrl:
  eissn: 1098-5549
  dateEnd: 20250403
  omitProxy: true
  ssIdentifier: ssj0006903
  issn: 1098-5549
  databaseCode: HH5
  dateStart: 19810101
  isFulltext: true
  titleUrlDefault: http://abc-chemistry.org/
  providerName: ABC ChemistRy
– providerCode: PRVAFT
  databaseName: Open Access Digital Library
  customDbUrl:
  eissn: 1098-5549
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0006903
  issn: 1098-5549
  databaseCode: KQ8
  dateStart: 19890101
  isFulltext: true
  titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html
  providerName: Colorado Alliance of Research Libraries
– providerCode: PRVAFT
  databaseName: Open Access Digital Library
  customDbUrl:
  eissn: 1098-5549
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0006903
  issn: 1098-5549
  databaseCode: KQ8
  dateStart: 19810101
  isFulltext: true
  titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html
  providerName: Colorado Alliance of Research Libraries
– providerCode: PRVBFR
  databaseName: Free Medical Journals
  customDbUrl:
  eissn: 1098-5549
  dateEnd: 20250403
  omitProxy: true
  ssIdentifier: ssj0006903
  issn: 1098-5549
  databaseCode: DIK
  dateStart: 19810101
  isFulltext: true
  titleUrlDefault: http://www.freemedicaljournals.com
  providerName: Flying Publisher
– providerCode: PRVFQY
  databaseName: GFMER Free Medical Journals
  customDbUrl:
  eissn: 1098-5549
  dateEnd: 20250403
  omitProxy: true
  ssIdentifier: ssj0006903
  issn: 1098-5549
  databaseCode: GX1
  dateStart: 19810101
  isFulltext: true
  titleUrlDefault: http://www.gfmer.ch/Medical_journals/Free_medical.php
  providerName: Geneva Foundation for Medical Education and Research
– providerCode: PRVAQN
  databaseName: PubMed Central
  customDbUrl:
  eissn: 1098-5549
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0006903
  issn: 1098-5549
  databaseCode: RPM
  dateStart: 19810101
  isFulltext: true
  titleUrlDefault: https://www.ncbi.nlm.nih.gov/pmc/
  providerName: National Library of Medicine
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFLa2Tmi8cBkMymD4gVdnjZ2LI_Eyuk0D1IoJKo0ny3YSLaJNAnWEyq_n2Gm6dgNxeaxiV_XJV5_v2Od8B6FXDHxULjNJcs4kCWTMiPKlIjQHZyGpH6XaViOPxtH5JHh3GV5uoUFXC-OS9rUqvHI688riyuVW1jN91OWJHflWwS3ZRjuRvVLqoZ3J-MPxZ3eUEg8IANYVFMEmTIA8uktlK5kJXjPpEnkoP5pp5VHm-dwDDx2RCGiL0wbd9E6dYvANGdNfkdHbOZW7TVnLxXc5na45rLP76KJbapun8sVrjPL0jxsqkP9iiwfo3pK94uP2yUO0lZV76E7bz3Kxh3aHXfu4R6geW6XkSi9MVQNDnxUaf7xqjLHl77jKcR0y_HaOT-e2-gn-BBhWjkcnI0pGrntIluLh2twTK2rR9n_CqjF4XBk8UcXXpjBFe6D5GE3OTj8Nz8myvQPRwDENkYonPNehz1KryRizXKUZDSVNEwgiNQRCeR6r3H6U2hJFOZA6YzmEA8q3G8c-6pVVmT1FmCcpVTThA6mAriQ6ySDiz7IA4rVQh6nuo7h7rUIvtc9tC46pcDEQ5WI0fCMoEz4XFhDCAsJ26GR95K9m1q3-x1_MOeiQI8BGAsC2Nq6PXq-DSRh3MpO3bVQE-_OXv-zAJ-CN2usdWWZVM4ehnPlA934_ImYhmJbCT3jSgvV6STQJgiDifRRtwHg1wKqQbz4BQDo18haDfURXeL9lqE0DXK_l2f9MOkB3XUKly_N7jnrmW5O9AGJo1CHafn_BD5c7wk9ljVuH
linkProvider Unpaywall
linkToUnpaywall http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFLZGJ7S9cBkMyrj4gVenjZ2rxMvoNg2kViCoNJ4s24m1iDbJqCNUfj3HTtO1G4jLYxW7qk---nzHPuc7CL1m4KO0yAXRCRMkEDEj0heSUA3OQlA_ypStRh5PovNp8P4ivNhBw64WxiXtK1l45WzulcWly62s52rQ5YkNfKvglt5Bu5G9Uuqh3enkw_EXd5QSDwkA1hUUwSZMgDy6S2UrmQleM-0SeWgymCvpUeb5iQceOiIR0BanDbrtnTrF4Bsypr8io7dzKveashbL72I223BYZ_fRx26pbZ7KV68x0lM_bqhA_ostHqB7K_aKj9snD9FOXh6gu20_y-UB2ht17eMeoXpilZIrtTRVDQx9Xij86bIxxpa_40rjOmT43QKfLmz1E_wJMKwcj0_GlIxd95A8w6ONuSdW1KLt_4RlY_CkMngqi6umMEV7oPkYTc9OP4_Oyaq9A1HAMQ0RMkkTrUKfZVaTMWZaZjkNBc1SCCIVBEJax1Lbj0JZoiiGQuVMQzggfbtxHKJeWZX5U4STNKOSpslQSKArqUpziPjzPIB4LVRhpvoo7l4rVyvtc9uCY8ZdDEQTPh695ZRxP-EWENwCwnboZH3kr2fWrf7HX8w56pDDwUYcwLYxro_ebIKJG3cyo9s2Kpz9-ctfdeDj8Ebt9Y4o86pZwNCE-UD3fj8iZiGYlsJPeNKC9XpJNA2CIEr6KNqC8XqAVSHffgKAdGrkLQb7iK7xfstQ2wa4Xsuz_5l0hPZdQqXL83uOeuZbk78AYmjky9Ve8BNGAFqS
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Nucleocytoplasmic+Shuttling+of+p53+Is+Essential+for+MDM2-Mediated+Cytoplasmic+Degradation+but+Not+Ubiquitination&rft.jtitle=Molecular+and+cellular+biology&rft.au=O%27Keefe%2C+Kevin&rft.au=Li%2C+Huiping&rft.au=Zhang%2C+Yanping&rft.date=2003-09-01&rft.pub=Taylor+%26+Francis&rft.eissn=1098-5549&rft.volume=23&rft.issue=18&rft.spage=6396&rft.epage=6405&rft_id=info:doi/10.1128%2FMCB.23.18.6396-6405.2003&rft.externalDocID=12267586
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0270-7306&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0270-7306&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0270-7306&client=summon