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Review
. 2014 Sep;19(9):1498-502.
doi: 10.1016/j.drudis.2014.07.009. Epub 2014 Jul 21.

The emerging role of speckle-type POZ protein (SPOP) in cancer development

Ram-Shankar Mani  1
Affiliations
Review

The emerging role of speckle-type POZ protein (SPOP) in cancer development

Ram-Shankar Mani. Drug Discov Today. 2014 Sep.

Abstract

Speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) is an E3 ubiquitin ligase adaptor protein that is frequently mutated in prostate and endometrial cancers. All the cancer-associated SPOP mutations reported to date are clustered in the meprin and TRAF (Tumor necrosis factor receptor-associated factor) homology (MATH) domain, presumably affecting substrate binding. SPOP mutations in prostate cancer are mutually exclusive with the ETS (Erythroblast transformation-specific) family gene rearrangements and define a distinct molecular subclass of prostate cancer. SPOP mutations contribute to prostate cancer development by altering the steady-state levels of key components in the androgen-signaling pathway.

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Conflict of interest statement

Conflict of interest

The author has no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Schematic representation of the speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) protein. The various domains are shown as boxes. The locations of amino acid residues mutated in prostate and endometrial cancers are shown.
Figure 2
Figure 2
Proposed mechanism for the role of speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) mutations in prostate cancer. Wild-type SPOP binds to its substrates, which are then targeted for ubiquitin-mediated degradation by the SPOP-Cullin 3-RING box 1 ubiquitin ligase and E2 conjugating enzyme (a). Mutations in SPOP, which block its interaction with the substrate (b), or substrate mutations that block the interaction with SPOP (c), help the substrate to escape from ubiquitin-mediated degradation.
See this image and copyright information in PMC

References

    1. Hershko A, et al. Basic Medical Research Award. The ubiquitin system. Nat Med. 2000;6:1073–1081. - PubMed
    1. Pei XH, et al. Cytoplasmic CUL9/PARC ubiquitin ligase is a tumor suppressor and promotes p53-dependent apoptosis. Cancer Res. 2011;71:2969–2977. - PMC - PubMed
    1. Petroski MD, Deshaies RJ. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol. 2005;6:9–20. - PubMed
    1. Ascoli CA, Maul GG. Identification of a novel nuclear domain. J Cell Biol. 1991;112:785–795. - PMC - PubMed
    1. Andrade LE, et al. Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80-coilin. J Exp Med. 1991;173:1407–1419. - PMC - PubMed

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