The mechanism of c-Myc expression regulated by T cell protein p80

Abstract:

Our experimental data indicate that overexpression of p80 in p80 null T cell leukemia cells significantly down regulates c-Myc oncoprotein and blocks cell cycle progression from G1 to S phase. The qPCR examination and protein stability test found that p80 regulates expression of c-Myc at the transcriptional level. The analysis of c-Myc promoter activity at the presence of p80 by Dual Luciferase Reporter Assay indicated that the transcriptional repression of p80 on c-Myc promoter is located at -1042bp~-630bp above the transcription start site of cMyc gene. The transcription factor binding sites search of this region by software TFSEARCH revealed multiple binding sequences of c-Myb, another oncoprotein and transcription factor which plays an important role in the proliferation and differentiation of blood cells during hematopoiesis. Knockdown c-Myb in MOLT-4 cells stably expressing p80 indicate that p80 suppresses the transcription of c-Myc gene through c-Myb. Co-immunoprecipitation experiment demonstrated that p80 interacts with c-Myb inside cells. The further experiment has shown that transcriptional repression of c-Myc by p80 is dependent on the enzymatic activity of histone deacetylase. Taken together, our results suggest that p80 recruits histone deacetylase to the c-Myc promoter through interaction with transcription factor c-Myb, and p80 suppresses c-Myc expression by histone deacetylation.