FLASH Binds p53 and Enhances its Transcriptional Activity / 中国生物化学与分子生物学报

ABSTRACT

As an important transcription factor, the tumor suppressor protein p53 is involved in multiple biological processes such as cell cycle regulation, cell division, cell senescence and DNA repair The functional roles of p53 under various physiological conditions are inseparable from the assistance of many cofactors, which can regulate the protein modification, cellular sub-localization, and protein stability of p53 Therefore, the identification of p53-binding protein(s) has important biological significance for further understanding the signal transduction network of p53 in vivo. In the present study, a novel p53-binding protein, FADD-like interleukin-1β-converting enzyme associated huge protein (FLASH) was identified through a yeast two-hybrid screen The protein-protein interaction and the structural basis of the interaction between FLASH and p53 was also confirmed by co-immunoprecipitation analysis These studies have shown that p53 can simultaneously interact with both FLASH-N1 (aa 1 ~ 200) and FLASH-C1 (aa 1 534 ~ 1 780) In addition, both of FLASH-N and FLASH-C can interact with the same region of p53 (aa 293 ~ 393) Transcription analysis has revealed that the full length of FLASH and FLASH-M (aa 921 ~ 1533) can enhance the transcription activity of p53 In summary, FLASH can bind to p53 and enhance its transcriptional activity