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CARF is a multi-module regulator of cell proliferation and a molecular bridge between cellular senescence and

Renu Wadhwa1, Rajkumar Singh Kalra1, Sunil C Kaul1

  • 1DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305 8565 Japan.

Mechanisms of Ageing and Development
|July 30, 2017
PubMed

Insights

Collaborator of ARF (CARF) protein stabilizes p53, impacting cell fate. CARF levels dictate whether cells undergo senescence, proliferation, or apoptosis, influencing DNA damage response and cancer development.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Collaborator of ARF (CARF) is an Alternative Reading Frame (ARF)-interacting protein.
  • CARF influences the stability of the p53 tumor suppressor protein.
  • CARF regulates the HDM2-p53 negative feedback loop.

Purpose of the Study:

  • To comprehensively review the molecular mechanisms of CARF functions.
  • To elucidate CARF's role in DNA damage response, cell cycle, and cell death pathways.
  • To discuss how CARF levels influence cellular fate, including senescence and malignant transformation.

Main Methods:

  • Yeast two-hybrid screening for ARF-interacting proteins.
  • Analysis of CARF's effect on p53 protein stability.
  • Investigation of CARF's transcriptional activity on HDM2.
  • Assessment of cell phenotypes in response to CARF overexpression and compromise.

Main Results:

  • CARF stabilizes p53 through ARF-dependent and -independent pathways.
  • CARF represses HDM2 transcription, preventing p53 degradation.
  • CARF levels determine cell fate: overexpression leads to growth arrest, while compromised CARF induces apoptosis.
  • CARF regulates the p53-HDM2-p21WAF1 axis, impacting cell proliferation.

Conclusions:

  • CARF plays a critical role in regulating DNA damage response and cell fate.
  • The threshold of CARF levels is a key determinant of cellular outcomes, from senescence to malignant transformation.
  • Understanding CARF's function provides insights into potential therapeutic strategies for cancer.
Keywords:
CARFMalignant transformationOverexpressionSenescenceSuperexpression

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