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Human U3 protein 14a plays an anti-apoptotic role in cancer cells

Teng Ma1, Chenxi Lu1, Yafei Guo1

  • 1.

Biological Chemistry
|July 5, 2017
PubMed

Insights

Human U three protein 14a (hUTP14a) protects tumor cells from apoptosis via a p53-independent pathway. Its down-regulation precedes apoptosis, suggesting hUTP14a is a potential anti-tumor therapy target.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Human U three protein 14a (hUTP14a) is known to bind and promote p53 degradation.
  • The role of hUTP14a in tumor cell survival and apoptosis remains incompletely understood.

Purpose of the Study:

  • To investigate the role of hUTP14a in tumor cell apoptosis, particularly in response to chemotherapy.
  • To elucidate the mechanism by which hUTP14a influences apoptosis and its potential as a therapeutic target.

Main Methods:

  • Knockdown of hUTP14a using RNA interference.
  • Induction of apoptosis using chemotherapeutic drugs and irradiation.
  • Western blot analysis to assess protein levels.
  • Treatment with pan-caspase inhibitor z-VAD-FMK.
  • Ectopic expression of hUTP14a.

Main Results:

  • Knockdown of hUTP14a activated the intrinsic apoptosis pathway and sensitized tumor cells to chemotherapy.
  • hUTP14a protein levels decreased upon chemotherapy or irradiation-induced apoptosis, independent of caspase activity.
  • Ectopic expression of hUTP14a conferred protection against chemotherapeutic drug-induced apoptosis.
  • hUTP14a functions independently of p53 in mediating anti-apoptotic effects.

Conclusions:

  • hUTP14a plays a significant anti-apoptotic role in tumor cells through a p53-independent mechanism.
  • The down-regulation of hUTP14a is an early event in apoptosis.
  • hUTP14a represents a promising therapeutic target for enhancing anti-tumor therapies.
Keywords:
apoptosishUTP14aintrinsic pathway of apoptosisp53-independent

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