DNAJB1 stabilizes MDM2 and contributes to cancer cell proliferation in a p53-dependent manner

Min Qi1, Jianglin Zhang2, Weiqi Zeng2

  • 1Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.

Insights

DNAJB1 stabilizes MDM2, inhibiting p53 degradation and activating the p53 pathway. This DNAJB1 function suppresses tumor growth in a p53-dependent manner, highlighting its role in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Protein Interactions

Background:

  • MDM2 and MDMX are key regulators of the tumor suppressor p53.
  • Their distinct roles in p53 regulation require further elucidation.

Purpose of the Study:

  • To identify novel proteins interacting with MDM2.
  • To characterize the functional relationship between DNAJB1 and MDM2 in the context of p53 regulation.

Main Methods:

  • Yeast two-hybrid (Y2H) screening using the MDM2 acidic domain.
  • In vitro and in vivo binding assays.
  • Western blotting to assess protein stability and ubiquitination.
  • Cellular assays to evaluate pathway activity and cell growth.
  • RNA interference (siRNA) and viral protein expression (HPV E6).

Main Results:

  • DNAJB1 specifically binds to MDM2, not MDMX.
  • DNAJB1 enhances MDM2 stability at the post-translational level.
  • DNAJB1 inhibits MDM2-mediated ubiquitination and degradation of p53.
  • Depletion of DNAJB1 activates the Rb/E2F pathway and promotes cancer cell growth, dependent on p53.
  • HPV E6 or p53 siRNA abrogates the effects of DNAJB1 depletion.

Conclusions:

  • DNAJB1 is a novel MDM2-interacting protein.
  • DNAJB1 functions as a p53-dependent tumor suppressor by stabilizing MDM2 and promoting p53 activity.
  • Targeting DNAJB1 may offer therapeutic strategies in cancer treatment.

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