SPOP is essential for DNA replication licensing through maintaining translation of CDT1 and CDC6 in HaCaT cells

Sayoko Sanada, Masashi Maekawa, Sota Tate, Hiroki Nakaoka, Yasuhiro Fujisawa, Koji Sayama, Shigeki Higashiyama

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Speckle-type pox virus and zinc finger (POZ) protein (SPOP), a substrate recognition receptor for the cullin-3/RING ubiquitin E3 complex, leads to the ubiquitination of >40 of its target substrates. Since a variety of point mutations in the substrate-binding domain of SPOP have been identified in cancers, including prostate and endometrial cancers, the pathological roles of those cancer-associated SPOP mutants have been extensively elucidated. In this study, we evaluated the cellular functions of wild-type SPOP in non-cancerous human keratinocyte-derived HaCaT cells expressing wild-type SPOP gene. SPOP knockdown using siRNA in HaCaT cells dramatically reduced cell growth and arrested their cell cycles at G1/S phase. The expression of DNA replication licensing factors CDT1 and CDC6 in HaCaT cells drastically decreased on SPOP knockdown as their translation was inhibited. CDT1 and CDC6 downregulation induced p21 expression without p53 activation. Our results suggest that SPOP is essential for DNA replication licensing in non-cancerous keratinocyte HaCaT cells.

Original languageEnglish
Pages (from-to)30-38
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume651
DOIs
Publication statusPublished - 2023 Apr 9
Externally publishedYes

Keywords

  • CDC6
  • CDT1
  • DNA replication licensing
  • SPOP
  • Translation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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