The Interaction Of THAP11and ABRO1and Their Mediated Biological Functions

Protein interactions play an important role in the protein biological function. Itmay provide clues to the function of the target proteins and is likely to reveal themolecular mechanism. THAP11, which is a zinc-dependent transcriptional factor ofTHAP protein families, is widely involved in cell apoptosis and proliferationregulation. Previous studies have found that THAP11can inhibit cell proliferation byinhibition of c-myc transcription. However, the mechanisms and biological functionsof THAP11still remain to be further studied. ABRO1(Abraxas Brother1), also knownas KIAA0157/FAM175B, is a scaffold protein of BRISC enzyme complex as well as amust composition of the complex to play the de-ubiquitination catalytic activity bychanging the conformation of BRCC36and promoting its catalytic activity.Furthermore, ABRO1can interact with THAP5and AP-1protein families and involvein cell oxidative stress reactions. Researches on ABRO1are still in its infancy, thecurrent information on ABRO1protein structure and its function mechanisms is stilllimited and needs further study.In order to further study THAP11and ABRO1proteins and biological functionsmediated by them, the immunoprecipitation technique is used to determine theinteraction of THAP11and ABRO1in vivo and in vitro and their interaction domains.THAP11and ABRO1are found to co-localized in the nucleus when DNA damaged byimmunofluorescence. Further studies are conducted in DNA damaged conditions andfound that DNA damages can up-regulate the protein expression of ABRO1andTHAP11and this up-regulation is p53-independent. ABRO1are found to be animportant gene to mediate DNA damage response and it suggests that THAP11mayinvolve in regulation of DNA damage. Therefore, cell apoptosis and cell cycle ofover-expression and interference THAP11lentivirus-infected cells in normal and DNAdamaged conditions were detected and found that THAP11over-expression canpromote apoptosis and lead to an obvious G2arrest. When DNA damaged, the G0/G1is arrested and the effect is enhanced in THAP11over-expressed one.Previous studies found that ABRO1interacts with p53and enhances the stabilityof p53.Considering my study that THAP11interacts with ABRO1and is involved in regulation of cellular response to DNA damage, we examined the interaction betweenTHAP11and p53and found that THAP11interacts with p53and stabilize p53byinhibiting the ubiquitination of p53. THAP11is found to have an effect on thetranscriptional activity of MDM2and p21respectively which are downstream targetedgenes of p53.This study reveals that THAP11is a novel p53regulatory protein. Further studiesare still needed to reveal the mechanism of cell cycle regulation and tumordevelopment...