The NUCKS1-SKP2-p21/p27 axis controls S phase entry.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34845229.
- Also identified by DOI 10.1038/s41467-021-27124-8 and PMC identifier 8630071.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>SKP2</sup> 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.
Medical subject headings
- Cell Transformation, Neoplastic
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclin-Dependent Kinase Inhibitor p27
- Nuclear Proteins
- Phosphoproteins
- S Phase
- S-Phase Kinase-Associated Proteins