The function of BAD, a proapoptotic member of the Bcl-2 family, is regulated primarily by rapid changes in phosphorylation that modulate its protein-protein interactions and subcellular localization. We show here that, during interleukin-3 (IL-3) deprivation-induced apoptosis of 32Dcl3 murine myeloid precursor cells, BAD is cleaved by a caspase(s) at its N terminus to generate a 15-kDa truncated protein. The 15-kDa truncated BAD is a more potent inducer of apoptosis than the wild-type protein, whereas a mutant BAD resistant to caspase 3 cleavage is a weak apoptosis inducer. Truncated BAD is detectable only in the mitochondrial fraction, interacts with BCL-X(L) at least as effectively as the wild-type protein, and is more potent than wild-type BAD in inducing cytochrome c release. Human BAD, which is 43 amino acids shorter than its mouse counterpart, is also cleaved by a caspase(s) upon exposure of Jurkat T cells to anti-FAS antibody, tumor necrosis factor alpha (TNF-alpha), or TRAIL. Moreover, a truncated form of human BAD lacking the N-terminal 28 amino acids is more potent than wild-type BAD in inducing apoptosis. The generation of truncated BAD was blocked by Bcl-2 in IL-3-deprived 32Dcl3 cells but not in Jurkat T cells exposed to anti-FAS antibody, TNF-alpha, or TRAIL. Together, these findings point to a novel and important role for BAD in maintaining the apoptotic phenotype in response to various apoptosis inducers.
Caspase cleveage enhances the apoptosis-inducing effects of BAD / Condorelli, F; Salomoni, P; Cottoret, S; Cesi, V; Srinivasula, Sm; Alnemri, Es; Calabretta, Bruno. - In: MOLECULAR AND CELLULAR BIOLOGY. - ISSN 0270-7306. - STAMPA. - 21(2001), pp. 3025-3036.
|Data di pubblicazione:||2001|
|Titolo:||Caspase cleveage enhances the apoptosis-inducing effects of BAD|
|Autore/i:||Condorelli, F; Salomoni, P; Cottoret, S; Cesi, V; Srinivasula, Sm; Alnemri, Es; Calabretta, Bruno|
|Codice identificativo ISI:||WOS:000168092600006|
|Codice identificativo Scopus:||2-s2.0-0035047712|
|Codice identificativo Pubmed:||11287608|
|Citazione:||Caspase cleveage enhances the apoptosis-inducing effects of BAD / Condorelli, F; Salomoni, P; Cottoret, S; Cesi, V; Srinivasula, Sm; Alnemri, Es; Calabretta, Bruno. - In: MOLECULAR AND CELLULAR BIOLOGY. - ISSN 0270-7306. - STAMPA. - 21(2001), pp. 3025-3036.|
|Tipologia||Articolo su rivista|
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