It has become increasingly clear that caspases, far from being merely cell death effectors, have a much wider range of functions within the cell. These functions are as diverse as signal transduction and cytoskeletal remodeling, and caspases are now known to have an essential role in cell proliferation, migration, and differentiation. There is also evidence that apoptotic cells themselves can direct the behavior of nearby cells through the caspase-dependent secretion of paracrine signaling factors. In some processes, including the differentiation of skeletal muscle myoblasts, both caspase activation in differentiating cells as well as signaling from apoptotic cells has been reported. Here, we review the non-apoptotic outcomes of caspase activity in a range of different model systems and attempt to integrate this knowledge.
Viruses co-evolve with their hosts, and many viruses have developed mechanisms to suppress or modify the host cell apoptotic response for their own benefit. Recently, evidence has emerged for the opposite strategy. Some viruses have developed the ability to co-opt apoptotic caspase activity to facilitate their own proliferation. In these strategies, viral proteins are cleaved by host caspases to create cleavage products with novel activities which facilitate viral replication. This represents a novel and interesting class of viral-host interactions, and also represents a new group of non-apoptotic roles for caspases. Here we review the evidence for such strategies, and discuss their origins and their implications for our understanding of the relationship between viral pathogenesis and programmed cell death.
Glycoprotein B (gB) is conserved among the herpesviruses and participates in both virus entry and cell-cell spread. The ER export of VZV gB is mediated by two cytoplasmic domain regions, aa 818-826, which contains a YXXphi motif, and the C-terminal 17 aa. The current study examines whether related sequences in the cytoplasmic domains of HSV-1 and HCMV gB similarly influence the ER export of their gB homologs. Directed mutations were introduced into the cytoplasmic domains of HSV-1 and HCMV gB, and the efficiencies with which the mutated proteins acquired Golgi-dependent modifications were determined. Sequences homologous to VZV gB aa 818-826 were required for normal ER export of both HSV-1 gB and HCMV gB. However, the C-terminal regions of HSV-1 and HCMV gB had no impact on ER export. Therefore, alpha- and betaherpesvirus gB homologs share conserved ER export signals, but species-specific differences in the ER export of gB also exist.
Caspases play central roles in mediating both cell death and inflammation. It has more recently become evident that caspases also drive other biological processes. Most prominently, caspases have been shown to be involved in differentiation. Several stem and progenitor cell types rely on caspases to initiate and execute their differentiation processes. These range from neural and glial cells, to skeletal myoblasts and osteoblasts, and several cell types of the hematopoietic system. Beyond differentiation, caspases have also been shown to play roles in other "noncanonical" processes, including cell proliferation, arrest, and senescence, thereby contributing to the mechanisms that regulate tissue homeostasis at multiple levels. Remarkably, caspases directly influence the course of the cell cycle in both a positive and negative manner. Caspases both cleave elements of the cell-cycle machinery and are themselves substrates of cell-cycle kinases. Here we aim to summarize the breadth of interactions between caspases and cell-cycle regulators. We also highlight recent developments in this area.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.