The NUCKS1-SKP2-p21/p27 Axis Controls S Phase Entry

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Nov 30

PMID 34845229

Citations 21

Authors

Samuel Hume

Claudia P Grou

Pauline Lascaux

Vincenzo DAngiolella

Arnaud J Legrand

Kristijan Ramadan

Grigory L Dianov

Affiliations

Soon will be listed here.

Abstract

Efficient entry into S phase of the cell cycle is necessary for embryonic development and tissue homoeostasis. However, unscheduled S phase entry triggers DNA damage and promotes oncogenesis, underlining the requirement for strict control. Here, we identify the NUCKS1-SKP2-p21/p27 axis as a checkpoint pathway for the G1/S transition. In response to mitogenic stimulation, NUCKS1, a transcription factor, is recruited to chromatin to activate expression of SKP2, the F-box component of the SCF ubiquitin ligase, leading to degradation of p21 and p27 and promoting progression into S phase. In contrast, DNA damage induces p53-dependent transcriptional repression of NUCKS1, leading to SKP2 downregulation, p21/p27 upregulation, and cell cycle arrest. We propose that the NUCKS1-SKP2-p21/p27 axis integrates mitogenic and DNA damage signalling to control S phase entry. The Cancer Genome Atlas (TCGA) data reveal that this mechanism is hijacked in many cancers, potentially allowing cancer cells to sustain uncontrolled proliferation.

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