MDM2 promotes genome instability by ubiquitinating the transcription factor HBP1.

ABSTRACT: Genome instability is a common feature of tumor cells, and the persistent presence of genome instability is a potential mechanism of tumorigenesis. The E3 ubiquitin ligase MDM2 is intimately involved in genome instability, but its mechanisms are unclear. Our data demonstrated that the transcription factor HBP1 is a target of MDM2. MDM2 facilitates HBP1 proteasomal degradation by ubiquitinating HBP1, regardless of p53 status, thus attenuating the transcriptional inhibition of HBP1 in the expression of its target genes, such as the DNA methyltransferase DNMT1 and histone methyltransferase EZH2, which results in global DNA hypermethylation and histone hypermethylation and ultimately genome instability. The repression of HBP1 by MDM2 finally promotes cell growth and tumorigenesis. Next, we tho

SUBMITTER: Cao Z 

PROVIDER: S-EPMC6756050 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature