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ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing

J Han1, Y-L Kim, K-W Lee

  • 1School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.

Cell Death and Differentiation
|May 7, 2013
PubMed

Insights

Zinc finger protein 313 (ZNF313) acts as an E3 ligase, degrading p21(WAF1) to promote cell cycle progression and suppress senescence. Its dysregulation is linked to human cancers.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Biology

Background:

  • The function of ZNF313, a protein encoded by a gene located at chromosome 20q13.13 with frequent genomic amplification in cancers, is largely unknown.
  • ZNF313 interacts with XIAP-associated factor 1 (XAF1), influencing XAF1 stability and proapoptotic activity.

Purpose of the Study:

  • To elucidate the biological function of ZNF313.
  • To investigate the role of ZNF313 in cell cycle regulation, differentiation, and senescence.
  • To determine the mechanism by which ZNF313 affects cell cycle inhibitors.

Main Methods:

  • Protein-protein interaction studies to identify ZNF313 interactors.
  • Ubiquitination assays to assess ZNF313's ligase activity.
  • Cell cycle analysis and senescence assays.
  • Western blotting to evaluate protein stability.

Main Results:

  • ZNF313 functions as an E3 ubiquitin ligase, specifically targeting p21(WAF1) for degradation via its RING domain, thereby activating cell cycle progression and inhibiting senescence.
  • ZNF313 destabilizes other cyclin-dependent kinase inhibitors (CKIs) including p27(KIP1) and p57(KIP2), but not the INK4 family members.
  • ZNF313 expression is cell cycle-regulated, peaking in late G1, and is induced by growth factors; its reduction is associated with senescence and differentiation, while its upregulation is common in cancer cells.

Conclusions:

  • ZNF313 is a novel E3 ligase that degrades p21(WAF1) and other CIP/KIP family members, playing a critical role in cell cycle control and senescence.
  • The alteration of ZNF313 expression and localization is implicated in the pathogenesis of human diseases, particularly cancers.
  • ZNF313's function as a regulator of cell cycle progression and senescence suggests its potential as a therapeutic target in cancer.

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