Words similar to nef
Example sentences for: nef
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For instance, HIV-1 infection is able to down-regulate major histocompatibility complex type I (MHC-I) by various different viral proteins, including Tat which represses the transcription of MHC-I, Vpu which retains nascent MHC-I chains in the endoplasmic reticulum, and Nef which can mediate selective internalization of MHC-I molecules from the plasma membrane.
10) have various expression levels of doubly spliced viral mRNAs, including Tat, Rev, Nef, Vpr, and other accessory proteins, we decided to perform the microarray in a system where Tat was constitutively expressed; asking whether Tat by itself, or in the absence of other accessory proteins, could still down-regulate host cellular genes.
[ 11 12 13 14 ] . Kidney transplants between normal and transgenic Tg26 siblings suggested that specific HIV-1 proteins within the kidney, and not circulating factors, transform infected renal epithelium [ 13 ] . Indeed, HIV-1 transgenic mice generated with an HIV-1 proviral construct mutated in the Nef "PXXP" SH3-binding motif for Src-family kinases failed to develop nephropathy [ 31 ] , and a recent in vitro analysis of podocytes infected with single gene mutants of HIV-1 further suggest that Nef plays a central role in causing the proliferative phenotype in HIVAN [ 8 ] . Utilizing these same single gene mutant viruses, we showed here that Nef appears to be play a role in the up-regulation of cyclin D 1 by HIV-1 in vitro . Importantly, these single gene mutants do not exclude the possibility that other HIV-1 gene(s) may cooperate with nef to induce cyclin D1, particularly
Analysis of cyclin D 1 transcript levels in podocytes infected with HIV-1 singly mutated with premature stop codons in the genes encoding the various structural and regulatory proteins of HIV-1 (except tat , which is present in every virus) showed that nef -deficient virus did not significantly up-regulate cyclin D 1 expression when compared to the other mutant viruses (Figure 5).
Cumulatively, however, these observations do suggest a mechanism whereby HIV-1 expression in renal epithelium may induce cyclin D 1 : activation of Src-family kinases by Nef would be expected to up-regulate cyclin D 1 gene expression and promote the synthesis and stabilization of cyclin D 1 protein via Src-Ras-MAPK and Src-PI3K-mTOR signal transduction pathways, respectively [ 32 33 34 ] . Interestingly, our unpublished in vitro observations and published data showing marked expression of basic fibroblast growth factor in the interstitium of HIVAN kidneys [ 35 ] suggest that soluble mitogens may be important cofactors with HIV-1 expression to induce cyclin D 1 . Thus, interrupting HIV-1 gene expression should down-regulate cyclin D 1 and correct the phenotypic abnormalities in infected podocytes.
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