In this examine, we have first dealt with the different modes and pathways involved in cell death and then we have focused on the regulation of several proteins in these signaling cascades by the different deubiquitinating enzymes, in the perspective of cancer. in a rather nascent stage with limited knowledge both and Apoptosis may occur during embryonic development, in mature tissues like thymus or under pathological conditions. The cardinal features of apoptosis include membrane blebbing, rounding up of cells, reduction of cell volume, chromatin condensation, and nuclear fragmentation. This follows either a caspase-dependent or caspase-independent pathway, which may or may not be associated with mitochondrial and/or immunological involvement, based on intrinsic or extrinsic cues. Necrosis generally occurs as a response to physical cellular injury and is mostly associated with pathological conditions. Necrosis is characterized by gain in cell volume, swelling of organelles, rupture of plasma membrane, and elicitation of inflammatory tissue response. Necrosis was initially thought to be an uncontrolled (accidental) death process, but recent evidences of well-defined signaling pathways involved in necrosis are coming into focus. Thus, programmed necrosis also known as necroptosis, exists as a back-up system for the cell when apoptosis is inhibited . Autophagy is a prosurvival strategy for the cells in cases of stress like nutrient or growth factor deprivation or cytokine-induction. The mode of action is Mouse monoclonal to IgG2a Isotype Control.This can be used as a mouse IgG2a isotype control in flow cytometry and other applications via sequestration of cytoplasmic material within autophagosomes for lysosomal degradation, with AZD8835 the absence of chromatin condensation, generally mediated by the autophagy genes (ATGs) [4, 28]. Hence, activation of autophagy under cellular stress has a cytoprotective outcome to maintain cellular homeostasis and inhibiting AZD8835 it may lead to cell death. This may again cause inhibition of developmental cell death indicating a role of autophagy in cell death. Therefore, the decision of whether autophagy results in cell survival or death depends on the context . Pyroptosis involves caspase-1 mediated cell death, an atypical caspase-dependent mechanism seen in monocytes, macrophages, and dendritic cells in case of microbial infection with implications in host defence [26, 30]. Paraptosis is cytoplasmic vacuolization initiated by swelling of mitochondria and ER. The response is mediated by mitogen-activated protein kinases (MAPKs) . Mitotic catastrophe is a process occurring in the absence of complete mitosis. It is characterized by multinucleated enlarged cells  and generally marked as a cellular strategy to combat genomic instability, which is very common in cancer. The major factors involved are cell cycle-dependent kinases such as cyclin-dependent kinase 1 (cdk1), aurora kinase B, polo-like kinases (Plks); cell cycle checkpoint proteins (Chk1 and 2, p53, and Rb); Bcl-2 family proteins; and caspases . The outcome of senescence in cells can be visualized by tumor suppression or promotion, aging, and tissue repair, because the process is associated with inhibition of cell proliferation, aging, and cell death . Cellular senescence can occur during irreversible cell cycle arrest upon encountering oncogenic stress, wherein cells become flattened, highly vacuolated, and heterochromatinized and form autophagosomes. The key players are PTEN, p53, p21, p16, and so forth . In the somatic cells, telomere shortening occurs with each replicative cycle, leading to replicative senescence and ultimately cell death which may be partially due to elicitation of DNA damage response signaling. It is the normal process of aging resulting from loss of clonogenic AZD8835 potential. But almost 85% of human cancers show enhanced expression of telomerases  accounting partially for immortalization of the cancer cells. Culture stress, like substrata, serum, oxidative stress, and so forth, may also lead to senescence inin vitrosettings [33, 35]. 2.2. Pathways Involved in Cell Death and Their Components For better understanding of the molecular mechanisms of the various modes of cell death mentioned above, here we have discussed the different pathways and the factors that are the main players involved in executing the cellular fates (also see Figure 1). As mentioned earlier, several signaling AZD8835 pathways are common in case of the cell death pathways and these involve various common players. The cellular response elicited may also overlap in certain cases. Hence, in this section, we have described the pathways one by one and intermittently discussed the AZD8835 involvement of the organelles in the specific contexts. 2.2.1. Intrinsic Cell Death Pathways The intrinsic death pathways are triggered by internal cellular cues and can generally be classified on the basis of their caspase dependency. Varied mitochondrial.