Speckle-type POZ protein
FunctionSpeckle-type POZ (pox virus and zinc finger) protein (SPOP) is an adaptor of the cullin-3-based ubiquitin ligase responsible for the degradation of oncoproteins which are overexpressed in many tumor cells[1]. SPOP forms nuclear foci after DNA damage at DNA double-strand break sites. SPOP interacts with bromodomain proteins via their MATH (Meprin And TRAP Homology) domain and regulate them. DiseaseSPOP mutations contribute to prostate cancer development by altering the steady-state levels of key components in the androgen-signaling pathway [2]. Structural highlightsThe 3D structure of SPOP MATH domain complex with bromodomain (BRD3) peptide shows the with the prostate cancer-associated mutations located at SPOP residues forming H-bonds or hydrophobic contacts with BRD3 and the endometrial-associated (uterus-associated) [3]. 3D structures of speckle-type POZ protein |
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ReferencesReferences
- ↑ Zhang D, Wang H, Sun M, Yang J, Zhang W, Han S, Xu B. Speckle-type POZ protein, SPOP, is involved in the DNA damage response. Carcinogenesis. 2014 Aug;35(8):1691-7. doi: 10.1093/carcin/bgu022. Epub 2014 Jan , 22. PMID:24451148 doi:http://dx.doi.org/10.1093/carcin/bgu022
- ↑ Mani RS. The emerging role of speckle-type POZ protein (SPOP) in cancer development. Drug Discov Today. 2014 Sep;19(9):1498-502. doi: 10.1016/j.drudis.2014.07.009., Epub 2014 Jul 21. PMID:25058385 doi:http://dx.doi.org/10.1016/j.drudis.2014.07.009
- ↑ Ostertag MS, Hutwelker W, Plettenburg O, Sattler M, Popowicz GM. Structural Insights into BET Client Recognition of Endometrial and Prostate Cancer-Associated SPOP Mutants. J Mol Biol. 2019 Apr 23. pii: S0022-2836(19)30213-X. doi:, 10.1016/j.jmb.2019.04.017. PMID:31026449 doi:http://dx.doi.org/10.1016/j.jmb.2019.04.017