Fusion LC3B-II levels offer only a snapshot of the number of autophagosomes in cells at one CX-4945 time-point and do not NVP-BEZ 235 Tosylate manufacturer indicate an up-regulation or down-regulation of autophagy in its entirety. Accordingly, a decrease in the numbers of autophagosomes in a cell can occur by a decrease in autophagosome formation or an increase in autophagosome degradation. Detection of other critical autophagy proteins like Beclin-1 can offer further insight into the activation of autophagy within these cells. This protein is involved in both the signaling pathway activating autophagy and in the initial step of autophagosome formation. Currently there is no evidence suggesting a role for IAPs in the regulation of autophagy in humans. The BIRC6 protein is at 528 kDa, an unusually large member of the IAP family. It consists of a single N-terminal BIR domain and a C-terminal ubiquitin-conjugating domain; the latter has chimeric E2/E3 ubiquitin ligase activity as well as antiapoptotic activity. Through its BIR domain, BIRC6 is capable of binding to and inhibiting active caspases, including caspases-3, 6, 7 and 9 and such interactions have been shown to underlie BIRC6��s ability to inhibit the caspase cascade and ultimately apoptosis. Through its UBC domain, BIRC6 facilitates proteasomal degradation of pro-apoptotic proteins caspase-9, SMAC/DIABLO and HTRA2/OMI. BIRC6 is also a critical regulator of cytokinesis and hence plays an important role in cell proliferation. Recent evidence supports a widespread role for BIRC6 in conferring apoptosis resistance to cancer cells, as indicated by in vitro studies with cells from gliomas, lung cancers, cervical cancers, fibrosarcomas, osteosarcomas, breast cancers and colon cancers. In breast and lung cancer cells, apoptosis triggered by the loss of BIRC6 expression has been demonstrated to involve p53 stabilisation. BIRC6 expression in clinical cancer samples has been observed for colorectal cancer and childhood de novo acute myeloid leukemia. In the latter, elevated expression of BIRC6 mRNA was associated with an unfavourable response to chemotherapy and poor relapse-free survival rates. A role for BIRC6 in prostate cancer, however, has not been reported. In the present study, analysis of human prostate cancer cell lines and clinical specimens sho
