The Role Of Protein Kinase D1 In HIV-1 Replication

The Protein kinase D(PKD) enzymes,which comprise of three isoforms (PKD1/PKDμ,PKD2 and PKD3/PKDυ),are generally localized to the cytosol,but in stimulated cells,they are translocated to various subcellular compartments.These enzymes play numerous roles in a variety of normal and pathological processes including transcriptional response to mitochondrial oxidative stress,T-cell receptor signaling,cardiac gene expression and contractility,apoptosis and carcinogenesis. They are also involved in a number of cellular processes such as regulation of Golgi organisation,protein trafficking,Golgi vesicle fission,and are at the converging point of a number of signal pathways.In this study,we showed that although PKD1 is not expressed in HeLa cells,it could be ectopically expressed and was able to stimulate HIV luciferase activity. However,using deletions mutants of the HIV-1 LTR,we showed that induced expression of HIV-1 by PKD1 did not require TAR and did not also depend on the HIV LTR promoter.On the other hand,in 293T cells,knockdown of PKD1 resulted in the inhibition of HIV-1 expression.Similarly,we also showed that PKD1 did not activate P-TEFb,suggesting that PKD1 may not influence transcription elongation step.Finally,using qRT-PCR tool,we found that overexpresion of PKD1 did not influence the mRNA level of luciferase,suggesting that PKD1 had no effect on RNA transcription.Taken together,by transient transfected system,our results suggest that PKD1 may influence post-transcription steps and may also induce the accumulation of proteins.These findings therefore suggests some probable novel function(s) of PKD1 in cardiac hypertrophy.