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p27 as a Transcriptional Regulator: New Roles in Development and Cancer

Seyedeh Fatemeh Razavipour1, Kuzhuvelil B Harikumar2, Joyce M Slingerland3

  • 1Breast Cancer Program, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington DC.

Cancer Research
|April 29, 2020
PubMed

Insights

The protein p27, encoded by CDKN1B, regulates cell cycle, migration, and gene expression. Its noncanonical functions, particularly transcriptional regulation, are crucial in cancer development and progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The protein p27 (encoded by CDKN1B) is known to inhibit cyclin-CDK complexes, arresting cell cycle progression.
  • p27 also influences cell migration and development independently of its cell cycle inhibitory role.
  • CDKN1B mutations are rare in cancers, suggesting complex roles for p27 beyond tumor suppression.

Purpose of the Study:

  • To review the noncanonical, cyclin-dependent kinase (CDK)-independent functions of p27.
  • To emphasize the role of p27 in transcriptional regulation and its implications in cancer.
  • To explore how p27's interaction with transcription factors like cJun drives oncogenic pathways.

Main Methods:

  • Literature review focusing on CDK-independent functions of p27.
  • Analysis of recent data on p27's role in transcription and gene expression.
  • Examination of p27's phosphorylation-dependent interactions and their impact on cellular processes.

Main Results:

  • p27 acts as a transcriptional coregulator, notably with cJun.
  • C-terminal phosphorylation of p27 enhances its interaction with cJun, promoting oncogenic pathways.
  • Phosphorylated p27 can repress differentiation programs and drive cancer progression.
  • p27's noncanonical functions in migration, invasion, and gene expression are critical in cancer.

Conclusions:

  • p27 exhibits dual roles in cancer, acting as both a tumor suppressor and an oncogene.
  • Transcriptional regulation by p27, particularly its interaction with cJun, is a key mechanism in cancer.
  • Understanding p27-associated transcriptional complexes may reveal new therapeutic targets for cancer treatment.

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