Apoptosis

About: Apoptosis is a research topic. Over the lifetime, 115486 publications have been published within this topic receiving 4887151 citations. The topic is also known as: GO:0006915 & apoptotic cell death.

Emerging roles of caspase-3 in apoptosis

Abstract: Caspases are crucial mediators of programmed cell death (apoptosis). Among them, caspase-3 is a frequently activated death protease, catalyzing the specific cleavage of many key cellular proteins. However, the specific requirements of this (or any other) caspase in apoptosis have remained largely unknown until now. Pathways to caspase-3 activation have been identified that are either dependent on or independent of mitochondrial cytochrome c release and caspase-9 function. Caspase-3 is essential for normal brain development and is important or essential in other apoptotic scenarios in a remarkable tissue-, cell type- or death stimulus-specific manner. Caspase-3 is also required for some typical hallmarks of apoptosis, and is indispensable for apoptotic chromatin condensation and DNA fragmentation in all cell types examined. Thus, caspase-3 is essential for certain processes associated with the dismantling of the cell and the formation of apoptotic bodies, but it may also function before or at the stage when commitment to loss of cell viability is made.

A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD

Abstract: The homeostasis of animals is regulated not only by the growth and differentiation of cells, but also by cell death through a process known as apoptosis. Apoptosis is mediated by members of the caspase family of proteases, and eventually causes the degradation of chromosomal DNA. A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells. CAD is a protein of 343 amino acids which carries a nuclear-localization signal; ICAD exists in a long and a short form. Recombinant ICAD specifically inhibits CAD-induced degradation of nuclear DNA and its DNase activity. When CAD is expressed with ICAD in COS cells or in a cell-free system, CAD is produced as a complex with ICAD: treatment with caspase 3 releases the DNase activity which causes DNA fragmentation in nuclei. ICAD therefore seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity; caspases activated by apoptotic stimuli then cleave ICAD, allowing CAD to enter the nucleus and degrade chromosomal DNA.

A novel anti-apoptosis gene, survivin , expressed in cancer and lymphoma

Abstract: Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer by facilitating the insurgence of mutations and by promoting resistance to therapy Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger Present during fetal development, survivin is undetectable in terminally differentiated adult tissues However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic) Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3) These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma

Two CD95 (APO-1/Fas) signaling pathways

Abstract: We have identified two cell types, each using almost exclusively one of two different CD95 (APO‐1/Fas) signaling pathways. In type I cells, caspase‐8 was activated within seconds and caspase‐3 within 30 min of receptor engagement, whereas in type II cells cleavage of both caspases was delayed for ∼60 min. However, both type I and type II cells showed similar kinetics of CD95‐mediated apoptosis and loss of mitochondrial transmembrane potential (ΔΨ m ). Upon CD95 triggering, all mitochondrial apoptogenic activities were blocked by Bcl‐2 or Bcl‐x L overexpression in both cell types. However, in type II but not type I cells, overexpression of Bcl‐2 or Bcl‐x L blocked caspase‐8 and caspase‐3 activation as well as apoptosis. In type I cells, induction of apoptosis was accompanied by activation of large amounts of caspase‐8 by the death‐inducing signaling complex (DISC), whereas in type II cells DISC formation was strongly reduced and activation of caspase‐8 and caspase‐3 occurred following the loss of ΔΨ m . Overexpression of caspase‐3 in the caspase‐3‐negative cell line MCF7‐Fas, normally resistant to CD95‐mediated apoptosis by overexpression of Bcl‐x L , converted these cells into true type I cells in which apoptosis was no longer inhibited by Bcl‐x L . In summary, in the presence of caspase‐3 the amount of active caspase‐8 generated at the DISC determines whether a mitochondria‐independent apoptosis pathway is used (type I cells) or not (type II cells).