Smad1 Promotes Tumorigenicity and Chemoresistance of Glioblastoma by Sequestering p300 From p53.

ABSTRACT: Acetylation is critically required for p53 activation, though it remains poorly understood how p53 acetylation is regulated in glioblastoma (GBM). This study reveals that p53 acetylation is a favorable prognostic marker for GBM, regardless of p53 status, and that Smad1, a key negative regulator of p53 acetylation, is involved in this process. Smad1 forms a complex with p53 and p300, inhibiting p300's interaction with p53 and leading to reduced p53 acetylation and increased Smad1 acetylation in GBM. This results in enhanced tumor growth and resistance to chemotherapy, particularly in tumors with missense mutant p53. Acetylation of K373 is found to be essential for Smad1's oncogenic function but does not confer chemoresistance in the absence of p53. Through molecular docking, it is discovere

SUBMITTER: Gong L 

PROVIDER: S-EPMC11789598 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature