The roles of spop in dna damage response and dna replication

Masashi Maekawa, Shigeki Higashiyama

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


Speckle-type BTB/POZ protein (SPOP) is a substrate recognition receptor of the cullin-3 (CUL3)/RING type ubiquitin E3 complex. To date, approximately 30 proteins have been identified as ubiquitinated substrates of the CUL3/SPOP complex. Pathologically, missense mutations in the substrate-binding domain of SPOP have been found in prostate and endometrial cancers. Prostate and endometrial cancer-associated SPOP mutations lose and increase substrate-binding ability, respectively. Expression of these SPOP mutants, thus, causes aberrant turnovers of the substrate proteins, leading to tumor formation. Although the molecular properties of SPOP and its cancer-associated mutants have been intensively elucidated, their cellular functions remain unclear. Recently, a number of studies have uncovered the critical role of SPOP and its mutants in DNA damage response and DNA replication. In this review article, we summarize the physiological functions of SPOP as a “gatekeeper” of genome stability.

Original languageEnglish
Article number7293
Pages (from-to)1-13
Number of pages13
JournalInternational journal of molecular sciences
Issue number19
Publication statusPublished - 2020 Oct 1
Externally publishedYes


  • Cancer
  • Cullin-3
  • DNA damage response
  • DNA repair
  • DNA replication
  • Genome instability
  • SPOP
  • Topoisomerase

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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