Rabbit Anti-Human PDK1 (internal) Polyclonal antibody

Candidal infections are increasing at an alarming rate due to hospital acquired infections causing high mortality rates worldwide. Moreover, the emergence of drug resistant Candida strains is the major impediment against effective therapeutics. Thus, there is an imperious need to search for novel antifungal drug targets. Among various fungi, Candida albicans is one of the most prevalent human fungal pathogen. Protein kinases modify other signaling molecules through phosphorylation and transduce extracellular stimuli for adaptation ensuing C. albicans growth, persistence and pathogenesis. In C. albicans, there are various kinds of kinases such as MAP (Mitogen Activated Protein) kinase cascade involving Hog1 (High-osmolarity glycerol) and Cek1 (C. albicans ERK-like Kinasel) mediated pathways, cyclin dependent pathway, cAMP (cyclic adenosine monophosphate) -dependent protein kinase pathway and TOR signaling pathway. Herein we have reviewed the variety of functions served by protein kinases in C. albicans. Additionally, we have discussed the inhibitors for targeting these kinases. Together, we explore the potential of these kinases as effective drug target and discuss the progress made in the development of inhibitors against these targets.

Although the roles and underlying mechanisms of other PDK family members (i.e., PDK1, PDK2 and PDK3) in tumor progression have been extensively investigated and are well understood, the functions and underlying molecular mechanisms of pyruvate dehydrogenase kinase 4 (PDK4) in the tumorigenesis and progression of various cancers [including hepatocellular carcinoma (HCC)] remain largely unknown. In this study, we examined the expression profile of PDK4 in HCC clinical tissue specimens and the roles of PDK4 in the proliferation, tumorigenicity, motility and invasion of HCC cells. The immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) results revealed that PDK4 was significantly downregulated in the cohort of HCC clinical specimens. Additionally, PDK4 protein was found in both the nucleus and cytoplasm of HCC cells based on an immunofluorescence (ICC) assay, and PDK4 protein was also found in the nucleus and cytoplasm of cancer cells contained in HCC clinical specimens based on IHC. The CCK-8 assay and cell colony formation assay demonstrated that stable depletion of endogenous PDK4 by lentivirus-mediated RNA interference (RNAi) markedly promoted the proliferation of HCC cell lines (i.e., BEL-7402 and BEL-7404 cells) in vitro, while PDK4 silencing significantly enhanced the tumorigenic ability of BEL-7404 cells in vivo. In addition to enhance proliferation and tumorigenesis induced by PDK4 silencing, additional studies demonstrated that knockdown of PDK4 led to increase migration and invasion of BEL-7402 and BEL-7404 cells in vitro. Taken together, these findings suggest that the loss of PDK4 expression contributes to HCC malignant progression.