Stress signaling and Myc downregulation: implications for cancer.
The transcription factor Myc forms a complex with its partner Max and with the regulatory DNA sequences on its target genes. Formation of this complex is required for Myc functions and Myc-induced oncogenic transformation. We have recently shown that formation of the Myc/Max/DNA complex is inhibited by the stress-responsive protein kinase Pak2 signaling pathway through phosphorylation of Myc. As a consequence of the phosphorylation, Myc loses its gene activation activity and the ability to induce proliferation and cellular transformation. Additionally, phosphorylation induces degradation of the Myc protein. Activation of stress signaling pathways, including Pak2 activity, may be a potential therapeutic approach to block Myc-induced neoplasia.
Huang
Zhongdong
Z
The George Williams Hooper Foundation, University of California, San Francisco, 94143-0522, USA. huangzd@itsa.ucsf.edu
D050976:Basic-Leucine Zipper Transcription Factors; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D016147:Genes, Tumor Suppressor; D009369:Neoplasms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D054462:p21-Activated Kinases
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases