Ube2m drives hepatocellular cancer progression as a p53 negative regulator by binding to mdm2 and ribosomal protein l11

Ju Ha Kim, Jihoon Jung, Hyo Jung Lee, Deok Yong Sim, Eunji Im, Jieon Park, Woon Yi Park, Chi Hoon Ahn, Bum Sang Shim, Bonglee Kim, Sung Hoon Kim

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Though UBE2M, an E2 NEDD8-conjugating enzyme, is overexpressed in HepG2, Hep3B, Huh7 and PLC/PRF5 HCCs with poor prognosis by human tissue array and TCGA analysis, its underlying oncogenic mechanism remains unclear. Herein, UBE2M depletion suppressed viability and proliferation and induced cell cycle arrest and apoptosis via cleavages of PARP and caspase 3 and upregulation of p53, Bax and PUMA in HepG2, Huh7 and Hep3B cells. Furthermore, UBE2M depletion activated p53 expression and stability, while the ectopic expression of UBE2M disturbed p53 activation and enhanced degradation of exogenous p53 mediated by MDM2 in HepG2 cells. Interestingly, UBE2M binds to MDM2 or ribosomal protein L11, but not p53 in HepG2 cells, despite crosstalk between p53 and UBE2M. Consistently, the colocalization between UBE2M and MDM2 was observed by immunofluorescence. Notably, L11 was required in p53 activation by UBE2M depletion. Furthermore, UBE2M depletion retarded the growth of HepG2 cells in athymic nude mice along with elevated p53. Overall, these findings suggest that UBE2M promotes cancer progression as a p53 negative regulator by binding to MDM2 and ribosomal protein L11 in HCCs.

Original languageEnglish
Article number4901
JournalCancers
Volume13
Issue number19
DOIs
Publication statusPublished - 1 Oct 2021

Keywords

  • Hepatocellular carcinoma
  • MDM2
  • P53
  • Ribosomal protein L11
  • UBE2M

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