Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss of the oligodendrocyte (OL)-specific enzyme aspartoacylase (ASPA) from gene mutation results in the sponginess and loss of white matter (WM) in Canavan disease (CD). This study addresses the fate of OLs during the pathophysiology of CD in an adult ASPA knockout (KO) mouse strain. Massive arrays of neural stem/progenitor cells, immunopositive for PSA-NCAM, nestin, vimentin, and NG2, were observed within the severely affected spongy WM of the KO mouse brain. In these mice, G1-->S cell cycle progression was confirmed by an increase in cdk2-kinase activity, a reduction in mitotic inhibitors p21(Cip1) and p27(Kip1), and an increase in bromodeoxyuridine (BrdU) incorporation. Highly acetylated nuclear histones H2B and H3 were detected in adult KO mouse WM, suggesting the existence of noncompact chromatin as seen during early development. Costaining for BrdU- or Ki67-positive cells with markers for neural progenitors confirmed a continuous generation of OL lineage cells in KO WM. We observed a severe reduction in 21.5- and 18.5-kDa myelin basic protein and PLP/DM20 proteolipid proteins combined with a decrease in myelinated fibers and a perinuclear retention of myelin protein staining, indicating impairment in protein trafficking. Death of OLs, neurons, and astrocytes was identified in every region of the KO brain. Immature OLs constituted the largest population of dying cells, particularly in WM. We also report an early expression of full-length ASPA mRNA in normal mouse brain at embryonic day 12.5, when OL progenitors first appear during development. These findings support involvement of ASPA in CNS development and function.
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PMID:Lack of aspartoacylase activity disrupts survival and differentiation of neural progenitors and oligodendrocytes in a mouse model of Canavan disease. 1973 53

Since data-mining from the Oncomine database revealed that expression of histone H2B K120 monoubiquitin (H2Bub1) ligase RNF20 is decreased in metastatic prostate cancer, we elucidated the effect of RNF20 and its homolog RNF40 on androgen receptor (AR)-dependent transcription and prostate cancer cell growth. Both RNF20 and RNF40 were able to functionally and physically interact with the AR and modulate its transcriptional activity in intact cells. Chromatin immunoprecipitation analyses showed that the androgen induction of FKBP51 and PSA in LNCaP prostate cancer cells is accompanied with a dynamic increase in the H2Bub1 within the transcribed regions of these loci. Interestingly, depletion of RNF20 or RNF40 strongly retarded the growth of LNCaP cells, which was however unlikely to be due to altered androgen signaling, but due to decreased expression of several cell cycle promoters. Collectively, our results suggest that RNF20 and RNF40, either via ubiquitylation of H2B or other targets, are coupled to the proliferation of prostate cancer cells.
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PMID:Histone H2B ubiquitin ligases RNF20 and RNF40 in androgen signaling and prostate cancer cell growth. 2215 69