Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation.

By D. Nijhawan, M. Fang, E. Traer, Q. Zhong, Wenhua Gao, Fenghe Du, Xiaodong Wang. Genes & Development, 2003

628 citations recorded by the source corpus.

Ultraviolet (UV) irradiation of HeLa cells triggers an apoptotic response mediated by mitochondria. Biochemical analysis of this response revealed that the elimination of cytosolic inhibitors is required for mitochondrial release of cytochrome c and subsequent caspase activation. These inhibitors were found to be Mcl-1 and Bcl-xL, two antiapoptotic members of the Bcl-2 family. Following UV treatment, Mcl-1 protein synthesis is blocked, the existing pool of Mcl-1 protein is rapidly degraded by the proteasome, and cytosolic Bcl-xL translocates to the mitochondria. These events are sequential; the elimination of Mcl-1 is required for the translocation of Bcl-xL. The disappearance of Mcl-1 is also required for other mitochondrial apoptotic events including Bax translocation, cytochrome c release, and caspase activation.

Subfields: Developmental Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8eec55743854751a672f4c9440b84cbf9b72e6d8

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Citations in the corpus

The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. (2006, background): “One therapeutic strategy would be to combine ABT-737 with genotoxic agents, as several lead to Mcl-1 downregulation (Cuconati et al., 2003; Nijhawan et al., 2003; Willis et al., 2005), in part by p53-induced upregulation of Noxa (Shibue et al.”
Life in the balance: how BH3-only proteins induce apoptosis. (2005, background): “Mcl-1 had been implicated in Bak regulation by its formation of complexes with Bak [38 ] and its degradation early in apoptosis [39 ].”
Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. (2006, background): “This is consistent with a report that MCL-1 elimination is a prerequisite for BAX/BAK activation following UV radiation, preceding mitochondrial translocation of BAX and BCL-xL (Nijhawan et al., 2003).”
Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. (2005, background): “Pertinently, both Mcl-1 and Bcl-xL were identified biochemically as inhibitors of mitochondrial damage after DNA damage (Nijhawan et al. 2003), and we show that Bak is their critical, albeit probably not exclusive, target (see below).”
mir-29 regulates Mcl-1 protein expression and apoptosis (2007, background): “Either depletion of Mcl-1 (Nijhawan et al., 2003) or disruption of the interaction between Mcl-1 and Bak coincides with apoptosis following a cytotoxic stimulus (Leu et al., 2004).”
BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. (2005, methodology): “Cells were grown at 37 C Our results showed that the derepressor peptides to an OD600 of 0.8 and induced at room temperature overnight (Nijhawan et al., 2003).”
Ways of dying: multiple pathways to apoptosis. (2003, background): “1994), Mcl-1 is cytosolic (Nijhawan et al. 2003), and much of Bcl-w and Bcl-xL, like Bax, becomes tightly membrane-associated only after an allosteric change imposed by cytotoxic signals (Hsu et al.”
Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1 (2003, background): “and functions at an apical step in genotoxic death”
Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies (2006, background): “As BCL-X L and MCL-1 were identified as cytosolic inhibitors of mitochondrial permeabilization, and MCL-1 was proposed to play a pivotal role upstream of BAX translocatio”
The Bcl-2 apoptotic switch in cancer development and therapy (2007, background): “The Mcl-1 protein is particularly labile and is rapidly lost by proteasomal degradation early in response to several cytotoxic signals (Cuconati et al., 2003; Nijhawan et al., 2003).”