PAK4 signaling in health and disease: defining the PAK4–CREB axis

• Published in: Experimental & molecular medicine Vol. 51; no. 2; pp. 1 - 9
• Main Authors: Won, So-Yoon, Park, Jung-Jin, Shin, Eun-Young, Kim, Eung-Gook
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2019; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 13; 38; 631/378/1934; 631/80/86; 692/308/1426; Animals; Antineoplastic drugs; Antitumor agents; Biomedical and Life Sciences; Biomedicine; Cell adhesion; Cell adhesion & migration; Cell migration; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - metabolism; Disease Susceptibility; Drug development; Embryogenesis; Humans; Medical Biochemistry; Melanins - biosynthesis; Mesenchyme; Metastases; Molecular Medicine; Neoplasms - etiology; Neoplasms - metabolism; Neoplasms - pathology; Neuroprotection; p21-activated kinase; p21-Activated Kinases - chemistry; p21-Activated Kinases - metabolism; Parkinson Disease - etiology; Parkinson Disease - metabolism; Parkinson's disease; Prostate cancer; Protein Binding; Protein Interaction Domains and Motifs; Review; Review Article; Signal Transduction; Stem Cells; Therapeutic applications; 생화학
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/s12276-018-0204-0

p21-Activated kinase 4 (PAK4), a member of the PAK family, regulates a wide range of cellular functions, including cell adhesion, migration, proliferation, and survival. Dysregulation of its expression and activity thus contributes to the development of diverse pathological conditions. PAK4 plays a pivotal role in cancer progression by accelerating the epithelial–mesenchymal transition, invasion, and metastasis. Therefore, PAK4 is regarded as an attractive therapeutic target in diverse types of cancers, prompting the development of PAK4-specific inhibitors as anticancer drugs; however, these drugs have not yet been successful. PAK4 is essential for embryonic brain development and has a neuroprotective function. A long list of PAK4 effectors has been reported. Recently, the transcription factor CREB has emerged as a novel effector of PAK4. This finding has broad implications for the role of PAK4 in health and disease because CREB-mediated transcriptional reprogramming involves a wide range of genes. In this article, we review the PAK4 signaling pathways involved in prostate cancer, Parkinson’s disease, and melanogenesis, focusing in particular on the PAK4-CREB axis. Gene expression: The role of a regulatory enzyme in disease An enzyme that regulates an important controller of gene expression may offer a therapeutic target for cancer and other diseases. cAMP response element-binding protein (CREB) interacts with various other proteins to switch a myriad of target genes on and off in different cells. A review by Eung-Gook Kim, Eun-Young Shin and colleagues at Chungbuk National University, Cheongju, South Korea, explores the interplay between CREB and an enzyme called p21-activated kinase 4 (PAK4) in human health and disease. PAK4, for example, has been shown to promote CREB’s gene-activating function in prostate cancer, and PAK4 overexpression is a feature of numerous other tumor types. Disruptions in PAK4-mediated regulation of CREB activity have also been observed in neurons affected by Parkinson’s disease. The authors see strong clinical promise in further exploring the biology of the PAK4-CREB pathway.