BH3-only proteins of the Bcl-2 family regulate programmed cell death in mammals through activation of multidomain proapoptotic proteins Bax and Bak in response to various proapoptotic stimuli by mechanism that remains under dispute. Here, we report that the cell death-promoting activity of BH3-only proteins Bik, Bmf, Noxa, and tBid can only be reconstituted in yeast when both multidomain proapoptotic and antiapoptotic Bcl-2 family proteins are present. Inability of these proteins to induce cell death in the absence of antiapoptotic proteins suggests that all tested BH3-only proteins likely activate Bax and Bak indirectly by inhibiting antiapoptotic proteins.
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http://dx.doi.org/10.1111/1567-1364.12074 | DOI Listing |
Cell Death Dis
December 2024
Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215, Lodz, Poland.
Apoptosis-regulating proteins from the B-cell lymphoma-2 (BCL-2) family are of continued interest as they represent promising targets for anti-cancer therapies. Myeloid cell leukemia-1 (MCL-1), which usually refers to the long isoform (MCL-1L) is frequently overexpressed in various types of cancer. However, MCL1 pre-mRNA can also undergo alternative splicing through exon skipping to yield the short isoform, MCL-1S.
View Article and Find Full Text PDFNat Commun
October 2024
Research Department Cell and Developmental Biology, Division of Biosciences, University College London, London, UK.
Cell Death Differ
October 2024
Neuroscience Center; University of North Carolina, Chapel Hill, NC, USA.
Apoptosis is a fundamental process of all mammalian cells but exactly how it is regulated in different primary cells remains less explored. In most contexts, apoptosis is engaged to eliminate cells. However, postmitotic cells such as neurons must efficiently balance the need for developmental apoptosis versus the physiological needs for their long-term survival.
View Article and Find Full Text PDFCell Death Differ
October 2024
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
BCL-2 family proteins regulate apoptosis by initiating mitochondrial outer membrane permeabilization (MOMP). Activation of the MOMP effectors BAX and BAK is controlled by the interplay of anti-apoptotic BCL-2 proteins (e.g.
View Article and Find Full Text PDFMol Cancer
October 2024
Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, 200 First Street, S.W., Rochester, MN, 55905, USA.
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