Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313706737> ?p ?o ?g. }
- W4313706737 abstract "Spinal and bulbar muscular atrophy is caused by polyglutamine (polyQ) expansions in androgen receptor (AR), generating gain-of-function toxicity that may involve phosphorylation. Using cellular and animal models, we investigated what kinases and phosphatases target polyQ-expanded AR, whether polyQ expansions modify AR phosphorylation, and how this contributes to neurodegeneration. Mass spectrometry showed that polyQ expansions preserve native phosphorylation and increase phosphorylation at conserved sites controlling AR stability and transactivation. In small-molecule screening, we identified that CDC25/CDK2 signaling could enhance AR phosphorylation, and the calcium-sensitive phosphatase calcineurin had opposite effects. Pharmacologic and genetic manipulation of these kinases and phosphatases modified polyQ-expanded AR function and toxicity in cells, flies, and mice. Ablation of CDK2 reduced AR phosphorylation in the brainstem and restored expression of Myc and other genes involved in DNA damage, senescence, and apoptosis, indicating that the cell cycle-regulated kinase plays more than a bystander role in SBMA-vulnerable postmitotic cells." @default.
- W4313706737 created "2023-01-08" @default.
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- W4313706737 date "2023-01-06" @default.
- W4313706737 modified "2023-10-18" @default.
- W4313706737 title "Antagonistic effect of cyclin-dependent kinases and a calcium-dependent phosphatase on polyglutamine-expanded androgen receptor toxic gain of function" @default.
- W4313706737 cites W1563116834 @default.
- W4313706737 cites W1875122842 @default.
- W4313706737 cites W1966083586 @default.
- W4313706737 cites W1969342645 @default.
- W4313706737 cites W1975747878 @default.
- W4313706737 cites W1984754431 @default.
- W4313706737 cites W1985139403 @default.
- W4313706737 cites W1985902870 @default.
- W4313706737 cites W1987954645 @default.
- W4313706737 cites W1988278010 @default.
- W4313706737 cites W1999839154 @default.
- W4313706737 cites W2003707515 @default.
- W4313706737 cites W2011924190 @default.
- W4313706737 cites W2013452556 @default.
- W4313706737 cites W2024648144 @default.
- W4313706737 cites W2028703908 @default.
- W4313706737 cites W2033851432 @default.
- W4313706737 cites W2039144927 @default.
- W4313706737 cites W2043074724 @default.
- W4313706737 cites W2048826661 @default.
- W4313706737 cites W2049717808 @default.
- W4313706737 cites W2058127221 @default.
- W4313706737 cites W2063512792 @default.
- W4313706737 cites W2066150155 @default.
- W4313706737 cites W2067859370 @default.
- W4313706737 cites W2070385315 @default.
- W4313706737 cites W2072385327 @default.
- W4313706737 cites W2079817613 @default.
- W4313706737 cites W2084612997 @default.
- W4313706737 cites W2089473708 @default.
- W4313706737 cites W2091926537 @default.
- W4313706737 cites W2093161171 @default.
- W4313706737 cites W2104167786 @default.
- W4313706737 cites W2106072892 @default.
- W4313706737 cites W2110919845 @default.
- W4313706737 cites W2113333419 @default.
- W4313706737 cites W2113604152 @default.
- W4313706737 cites W2114113254 @default.
- W4313706737 cites W2117181237 @default.
- W4313706737 cites W2123332775 @default.
- W4313706737 cites W2128431731 @default.
- W4313706737 cites W2128633219 @default.
- W4313706737 cites W2131422252 @default.
- W4313706737 cites W2132844816 @default.
- W4313706737 cites W2133563625 @default.
- W4313706737 cites W2147688002 @default.
- W4313706737 cites W2153371047 @default.
- W4313706737 cites W2168974130 @default.
- W4313706737 cites W2169189097 @default.
- W4313706737 cites W2171020858 @default.
- W4313706737 cites W2289953129 @default.
- W4313706737 cites W2292334686 @default.
- W4313706737 cites W2412450093 @default.
- W4313706737 cites W2497027427 @default.
- W4313706737 cites W2567001142 @default.
- W4313706737 cites W2602011586 @default.
- W4313706737 cites W2734209854 @default.
- W4313706737 cites W2755245840 @default.
- W4313706737 cites W2762192100 @default.
- W4313706737 cites W2767869762 @default.
- W4313706737 cites W2769873544 @default.
- W4313706737 cites W2885299218 @default.
- W4313706737 cites W2936313629 @default.
- W4313706737 cites W2970215199 @default.
- W4313706737 cites W3003394053 @default.
- W4313706737 cites W3011893586 @default.
- W4313706737 cites W3087297916 @default.
- W4313706737 cites W3105512395 @default.
- W4313706737 cites W3159792978 @default.
- W4313706737 cites W3181933573 @default.
- W4313706737 cites W4226230232 @default.
- W4313706737 cites W4242614327 @default.
- W4313706737 cites W4293063502 @default.