Disease relevance of Psma1

• A study on the use of derivatized carbohydrates as C2-symmetric HIV-1 protease inhibitors has been undertaken [1].
• Proteasome expression in pectoral muscle followed a different pattern with increases in C2 and C5 and E2(14k) mRNA only being seen at weight losses above 17%, although muscle loss increased progressively with increasing weight loss [2].
• The AL2 gene found in members of the genus Begomovirus of the Geminiviridae encodes a transcriptional activator protein (TrAP; also known as AL2, AC2, or C2 protein) [3].

Psychiatry related information on Psma1

• Previous studies using post-mortem human brain extracts demonstrated that PrP in Creutzfeldt-Jakob disease (CJD) brains is cleaved by a cellular protease to generate a C-terminal fragment, referred to as C2, which has the same molecular weight as PrP-(27-30), the protease-resistant core of PrP(Sc) (1) [4].

High impact information on Psma1

• The integrity of a cholesterol-binding pocket in Niemann-Pick C2 protein is necessary to control lysosome cholesterol levels [5].
• Acidification of the medium with 1% serum did increase the mRNAs for ubiquitin and the C2 proteasome subunit, but when dexamethasone was added the mRNAs were increased significantly more [6].
• To investigate the linkage of C2 to the MHC a family of strain 2 X strain OM3 was studied: the C2B allotype segregated with the strain haplotype of OM3 whereas C2A1 does the same with the strain 2 haplotype [7].
• A strong linkage-disequilibrium between C2 and C4 allotypes was observed consisting of the pairs C2A1-C4F [7].
• In the guinea pig six common phenotypes for hemolytically active C2 were detected [7].

Biological context of Psma1

• Psma1 was mapped to mouse chromosome 7 using the interspecific backcross DNA panels from The Jackson Laboratory. Additional mapping studies showed that the mouse genes Psma1 and Pde3b are closely linked, residing between cM 53 and 53.3 in a region syntenic to human chromosome 11p15 [8].
• Linkage of total deficiency of the second component (C2) of the complement system and of genetic C2-polymorphism to the major histocompatibility complex of the guinea pig [7].
• Insulin suppressed levels of E2(14K) mRNA with an IC50 of 4 x 10(-9) M, but had no effects on mRNAs encoding polyubiquitin and proteasome subunits C2 and C8, which, like E2(14K), also increase in skeletal muscle upon fasting [9].
• We have examined the expression in bovine adrenal medulla of double C2 protein (DOC2), a vesicular protein which associates with intracellular phospholipid and Ca(2+) and is implicated in the modulation of regulated exocytosis [10].
• Treatment of C2 cells with AMP peptide protected monolayers against decreases in transepithelial electrical resistance induced by the oxidant monochloramine, indomethacin, or DSS [11].

Associations of Psma1 with chemical compounds

• PIF induced an increased expression of mRNA for proteasome alpha (C2) and beta (C5) subunits over the same concentration range as that inducing protein degradation and with a maximal effect 4 h after PIF addition [12].
• Strong phytogrowth-inhibition and cytotoxic activity were found with 1, 6, 11 and 16 with an acetylthio group at C-2, suggesting that the acetyl group seems to play an important role in both activities of alkyl 2-(acylthio)benzoates [13].
• Extension of ketone or hydroxyl substituents from the C2 position of the D-ring resulted in a 3-fold increase in binding affinity over the unsubstituted structure [14].
• MS revealed that these spots comprised apolipoprotein A1 (apoA1), apolipoprotein C3 (apoC3), vitamin D-binding protein, alpha-1-antitrypsin and proteasome subunit alpha type 1 [15].

Other interactions of Psma1

• The mouse Psma1 gene coding for the alpha-type C2 proteasome subunit: structural and functional analysis, mapping, and colocalization with Pde3b on mouse chromosome 7 [8].
• We have isolated and functionally characterized the mouse gene for the C2 subunit of the 20S proteasome [8].

Analytical, diagnostic and therapeutic context of Psma1

• 15(S)-hydroxyeicosatetraenoic acid also increased maximal expression of mRNA for proteasome subunits C2 and C5, as well as the ubiquitin-conjugating enzyme, E2(14k), after 4 h incubation, as determined by quantitative competitive RT-PCR [16].

References