Words similar to down-regulate
Example sentences for: down-regulate
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In comparison to the two general alternative mechanisms utilized by known transforming viruses to promote cell-cycle progression, namely, by activating or bypassing endogenous D-type cyclins (herein, referred to as "cyclin D"), it has not been established whether HIV-1 gene products trigger either cyclin D-dependent or cyclin D-independent proliferation in non-lymphoid tissues [ 15 ] . In infected renal epithelium, HIV-1 could disrupt the inhibitory binding of pRb to E2F independent of endogenous cyclin D, analogous to transforming viral mechanisms that bypass and down-regulate endogenous cyclin D, such as SV-40 T antigen binding to pRb [ 16 ] , HHV-8 v -cyclin binding to and activating cyclin-dependent kinase-6 (CDK) [ 17 ] , and activation of cyclin E by EBV-induced c -myc [ 18 ] . Alternatively, HIV-1 could activate cyclin D-dependent proliferation, as exemplified by RSV v -src-mediated signaling [ 19 ] . In most tissues, the selective activation of these cell-cycle pathways is readily discernable.
It should be noted that the fibroblast cells lines we used remain fully viable after detachment and transfer to suspension culture [ 31 43 ] . This is in contrast to most epithelial cells which undergo anoikis, i.e., apoptotic cell death after the disruption of cell-matrix interactions [ 45 ] . It is of interest that some anchorage-independent tumor cells, most of which are of epitheloid origin, become susceptible to anoikis after the introduction of exogenous PTEN [ 23 34 35 36 ] . These observations are in line with the established ability of PTEN to down-regulate the phosphatidylinositol 3-kinase (PI3-K)/PKB survival pathway [ 11 46 ] . The absence of anoikis in our two cell lines may reflect inherent cell type specific differences, i.e., the superior ability of fibroblasts to survive under suspension culture conditions.
First, PTEN's protein phosphatase activity is able to down-regulate focal adhesion kinase (FAK) phosphorylation, which leads to the inactivation of the Ras/MAP kinase pathway [ 19 20 21 ] . Second, its lipid phosphatase activity targets the second messenger phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P 3 ] and thereby blocks activation of the protein kinase B (PKB/Akt) pathway [ 11 18 22 23 24 ] . Whereas both of the above pathways are intimately involved in the control of cell growth and survival, PTEN-regulated FAK activity further appears to impinge on cell adhesion, cell migration, and cell invasion [ 20 21 ] . It therefore emerges that the loss of PTEN activity may confer increased survival ability, proliferative potential, and invasive capacity on cells, and thereby may promote progression towards a more malignant phenotype.
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.
Indeed, the use of a constitutively active mutant of PP1 has already been shown to result in pRB-dependent G1 arrest in human cancer cells [ 22 ] . Placing this mutant into the inducible expression system described here has the potential to down-regulate expression of wild-type endogenous PP1.
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