The NUCKS1-SKP2-p21/p27 axis controls S phase entry

Samuel Hume, Claudia P. Grou, Pauline Lascaux, Vincenzo D’Angiolella, Arnaud J. Legrand, Kristijan Ramadan, Grigory L. Dianov

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

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 SCFSKP2 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.

Язык оригиналаанглийский
Номер статьи6959
ЖурналNature Communications
Том12
Номер выпуска1
DOI
СостояниеОпубликовано - дек. 2021

Предметные области OECD FOS+WOS

  • 1.03 ФИЗИЧЕСКИЕ НАУКИ И АСТРОНОМИЯ
  • 1.04 ХИМИЧЕСКИЕ НАУКИ
  • 1.06 БИОЛОГИЧЕСКИЕ НАУКИ

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