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Sgt, Apoptosis And Cyclin D3 And Vdr Interaction Of Transcriptional Regulation Of Research

Posted on:2006-03-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:H Z WangFull Text:PDF
GTID:1110360155960360Subject:Biochemistry and Molecular Biology
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Part I: The research of the involvement of SGT in apoptosis The tetratricopeptide repeat(TPR) is a degenerate 34-amino acid repeat motif which is first discovered in CDC protein of yeast. This motif is widespread in evolution and is involved in a variety of cellular processes .SGT is a member of such TPR motif protein family, which is first identified as a binding partner of the nonstructural protein NS1 of parvovirus H-1. Next, GHR, Myostatin and Vpu protein were also found to interact with SGT. However, in a Caenorhabditis elegans model for Alzheimer disease, SGT may be involved in P-amyloid peptide-dependent pathogenicity in this model system. On the other hand, rat SGT promoted the chaperone activity of Hsc70 in a tripartite complex containing the cysteine string protein (Csp) and Hsc70, which is thought to participate in vesicle-mediated neuronal signal transduction. Most recently, a cellular function of SGT was associate with mitosis,In this study we reported that SGT plays a role in apoptotic signaling. Ectopic expression of SGT enhances DNA fragment and nucleus breakage after the induction of apoptosis. The increase of SGT mRNA is also observed in 7721 cells undergoing apoptosis, knockdown the expression of endogenous SGT contributes to the decrease of apoptosis of 7721 cells. Deletion analysis reveals that TPR domain is critical to proapoptotic function of SGT. Furthermore, we demonstrated that the PARP cleavage and cytochrome c release are enhanced when SGT is overexpressed in 7721 cells during apoptosis. Considering that SGT can regulate the chaperone activity of Hsc70 which can protect cell apoptosis, we therefore speculated whether the proapoptotic activity of SGT is dependent on Hsc70. However, to our disappointment , overexpression of Hsc70 could not inhibit the proapoptotic activity of SGT.
Keywords/Search Tags:SGT, Hsc70, apoptosis, TPR, RNAi, mitochondria, Cyclin D3, VDR, 1, 25(OH)2-D3, , transcriptional control
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