The Roles of SPOP in DNA Damage Response and DNA Replication.

Abstract:

: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.

journal_name

Int J Mol Sci

authors

Maekawa M,Higashiyama S

doi

10.3390/ijms21197293

subject

Has Abstract

pub_date

2020-10-02 00:00:00

issue

19

issn

1422-0067

pii

ijms21197293

journal_volume

21

pub_type

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