Disease relevance of SGTA

• UBP also interacts directly with HIV-1 Gag protein, the principal structural component of the viral capsid [1].
• We report here the identification of a novel cellular protein that interacts with NS1 from parvovirus H-1 and which we termed SGT, for small glutamine-rich tetratricopeptide repeat (TPR)-containing protein [2].
• Furthermore, overexpression of UBP in virus-producing cells resulted in a significant reduction in HIV-1 virion release [1].
• Double-stranded RNA inhibition of R05F9.10, the putative C. elegans ortholog of the human small glutamine-rich tetratricopeptide-repeat-containing protein (SGT), results in suppression of toxicity associated with A beta expression [3].
• PARTICIPANTS: The SGTP group consisted of 49 eyes of 49 consecutive patients with primary open-angle glaucoma with a history of glaucoma filtration surgery requiring glaucoma medical therapy and in need of cataract surgery, randomized to adjunctive MMC (SGTP MMC subgroup of 21 eyes) and no adjunctive MMC (SGTP control subgroup of 28 eyes) [4].
• Quantitative immunohistochemical analysis of alphaSGT and AR levels in a cohort of 32 primary and 64 metastatic human prostate cancers revealed dysregulation in the level of both proteins during disease progression [5].

High impact information on SGTA

• Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde [6].
• Affecting the function of a specific UBP in vivo could provide novel tools for controlling mammalian cell proliferation [7].
• The catalytic site of this enzyme class is similar to that found in UBP and UCH type ubiquitin proteases [8].
• Our results show that the guanine nucleotide exchange activity of full-length CSP is, in turn, regulated by Hsc70-SGT [9].
• We describe here an isoform of SGT with 60% amino acid sequence identity that we name betaSGT [10].

Biological context of SGTA

• Recent studies indicate that hSGT probably functions as a molecular chaperone involved in protein folding and processing [11].
• In conclusion, results obtained in this study demonstrate that hSGT protein is a constitutive component of all human cell lines tested and that this protein is essential for successful completion of cell division [12].
• Human SGT interacts with Bag-6/Bat-3/Scythe and cells with reduced levels of either protein display persistence of few misaligned chromosomes and mitotic arrest [13].
• Work presented here demonstrated the presence of human SGT (hSGT) protein in a panel of human cell lines and throughout the cell cycle [12].
• Analysis of HeLa cells expressing a histone 2A-YFP fusion protein revealed the continuous presence of few mislocalized chromosomes close to the spindle poles as possible cause for hSGT depletion-dependent prometaphase arrest [13].

Anatomical context of SGTA

• Association of Vpu-binding protein with microtubules and Vpu-dependent redistribution of HIV-1 Gag protein [14].
• Moreover, in the presence of SGT, the degradation of the transporter in reticulocyte lysates is inhibited [15].
• The aim of this study was to determine the expression of MT and SGTP in the bone marrow of patients with MPD [16].

Associations of SGTA with chemical compounds

• The increased nuclear localization of SGT was further confirmed by the Western blotting in GA-treated HeLa cells and H1299 cells [17].
• The C-terminal fragment of SGT indeed plays a role in the association of SGT with in vitro translated rat type 1 glucose transporter, an integral membrane protein folded in a non-physiological state [15].
• The product, which consists of 785 amino acids with a deduced molecular mass of 88.2 kDa, possesses His and Cys domains that are highly conserved in all members of the ubiquitin-specific processing (UBP) family of proteases [18].
• Solanidine UDP-glucose glucosyltransferase (SGT) is involved in the biosynthesis of steroidal glycoalkaloids in potatoes [19].
• Two protein bands corresponding to active forms of SGT (36 and 37 kDa) were excised and cleaved with cyanogen bromide in trifluoroacetic acid [19].

Physical interactions of SGTA

• hSGT interacts with the N-terminal region of myostatin [11].
• We found that GHR interacts with SGT [20].
• In this study, we reported that small glutamine-rich TPR-containing protein (SGT) interacted with not only Hsp90alpha but also Hsp90beta [17].

Other interactions of SGTA

• These findings suggest that hSGT may play a role in the regulation of myostatin secretion and activation [11].
• This negative effect of SGT/UBP on Hsc70 is similar in magnitude to that observed for the cochaperone CHIP [21].
• Thereby, Hsp70 and Bag-6/Bat-3/Scythe were identified as novel hSGT interaction partners while interaction with Hsc70 was confirmed [13].
• Inactivation of the ubiquitin-conjugating system did not affect the GHR-SGT interaction [20].
• Confocal analysis showed that treatment of cells with Hsp90-specific inhibitor geldanamycin (GA) disrupted the interaction of SGT with Hsp90beta and this contributed to the increase of nuclear localization of SGT in HeLa cells [17].

Analytical, diagnostic and therapeutic context of SGTA

• The physical interaction between hSGT and myostatin was further confirmed by pull-down and co-immunoprecipitation experiments [11].
• In H-1 virus-infected rat and human cells, compared to mock-infected controls, differences in the migration of SGT polypeptides were revealed after Western blot analysis of total cellular extracts [2].
• Most strikingly, depletion of hSGT led to reduced proliferation of the affected cell populations while the mitotic index was increased [12].
• Time-lapse video microscopy revealed that cells from hSGT-depleted populations were unable to complete cell division due to mitotic arrest which was frequently followed by cell death [12].
• SGT could be detected in both the nucleus and the cytoplasm of rat cells, as determined by indirect immunofluorescence analysis and Western blotting of fractionated cellular extracts with an affinity-purified antiserum raised against recombinant SGT (AC1.1) [2].

References