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A crucial role for PIH1D1 in modulating p53 stability via the R2TP complex

Singh, D. K.; Akhtar, Q.; Mir, R. A.

2026-02-09 biochemistry
10.64898/2026.02.07.704515 bioRxiv
Show abstract

The R2TP is a multimeric protein complex consists of RUVBL1, RUVBL2, PIH1D1, and RPAP3, and it is known to functions as a specialized co-chaperone. We hypothesize that PIH1D1 recognizes p53 and stabilizes it via R2TP complex. Upon successful completion of this study, innovative mechanism has been found for the interaction and stabilization of p53 and hence govern the cell cycle. Upon interaction between p53 and PIH1D1 protein, p53 is stabilized by PIH1D1 protein, without affecting its C-terminal domain. We have also observed that p53 protein levels were affected after the alteration in expression levels of PIH1D1. Based on the finding, we suggest that the R2TP complex stabilizes and regulates P53. Therefore, this novel method will work as a flashpoint to restore the function of p53 in cancer cells, controlling cancer and cell cycle progression.

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