P27 as a transcriptional regulator: New roles in development and cancer

Seyedeh Fatemeh Razavipour, Kuzhuvelil B. Harikumar, Joyce M. Slingerland

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

p27 binds and inhibits cyclin-CDK to arrest the cell cycle. p27 also regulates other processes including cell migration and development independent of its cyclin-dependent kinase (CDK) inhibitory action. p27 is an atypical tumor suppressor-deletion or mutational inactivation of the gene encoding p27, CDKN1B, is rare in human cancers. p27 is rarely fully lost in cancers because it can play both tumor suppressive and oncogenic roles. Until recently, the paradigm was that oncogenic deregulation results from either loss of growth restraint due to excess p27 proteolysis or from an oncogenic gain of function through PI3K-mediated C-terminal p27 phosphorylation, which disrupts the cytoskeleton to increase cell motility and metastasis. In cancers, C-terminal phosphorylation alters p27 protein-protein interactions and shifts p27 from CDK inhibitor to oncogene. Recent data indicate p27 regulates transcription and acts as a transcriptional coregulator of cJun. C-terminal p27 phosphorylation increases p27-cJun recruitment to and action on target genes to drive oncogenic pathways and repress differentiation programs. This review focuses on noncanonical, CDK-independent functions of p27 in migration, invasion, development, and gene expression, with emphasis on how transcriptional regulation by p27 illuminates its actions in cancer. A better understanding of how p27-associated transcriptional complexes are regulated might identify new therapeutic targets at the interface between differentiation and growth control.

Original languageEnglish (US)
Pages (from-to)3451-3458
Number of pages8
JournalCancer Research
Volume80
Issue number17
DOIs
StatePublished - Sep 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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