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Daxx deletion mutant (amino acids 501-625)-induced apoptosis occurs through the JNK/p38-Bax-dependent mitochondrial pathway.
J Cell Biochem. 2004 Aug 15; 92(6):1257-70.JC

Abstract

Death-associated protein (Daxx) deletion mutant (aa 501-625) has been known to be an inducer of apoptosis. In this study, we observed that the Bax-dependent mitochondrial death signaling pathway plays an important role in Daxx501-625-induced apoptosis. Daxx fragment-induced activation of caspase-9 and -3 was mediated through the apoptosis signal-regulating kinase 1 (ASK1)-MEK-c-Jun-N-terminal kinase (JNK)/p38-Bax pathway. By overexpressing JNK-binding domain (JBD) of JIP1, a JNK-inhibitory protein, and treatment with SB203580, a specific p38 inhibitor, DU-145 cells were made resistant to Daxx501-625-induced apoptosis. Capase-3 deficiency, Bax deficiency, or overexpression of a dominant-negative caspase-9 mutant prevented apoptosis, even though the Daxx501-625 fragment still activated the ASK1-MEK-MAPK pathway. Interestingly, Daxx501-625-induced Bcl-2 interacting domain (Bid) cleavage was suppressed in the dominant-negative caspase-9 mutant cells, whereas Bim was still phosphorylated in these cells. These results suggest that cleavage of Bid occurs downstream of caspase-9 activation. In contrast, phosphorylation of Bim is upstream of caspase-9 activation. Taken together, our results suggest that Daxx501-625-induced apoptosis is mediated through the ASK1-MEK-JNK/p38-Bim-Bax-dependent caspase pathway.

Authors+Show Affiliations

Department of Surgery and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15258908

Citation

Song, Jae J., and Yong J. Lee. "Daxx Deletion Mutant (amino Acids 501-625)-induced Apoptosis Occurs Through the JNK/p38-Bax-dependent Mitochondrial Pathway." Journal of Cellular Biochemistry, vol. 92, no. 6, 2004, pp. 1257-70.
Song JJ, Lee YJ. Daxx deletion mutant (amino acids 501-625)-induced apoptosis occurs through the JNK/p38-Bax-dependent mitochondrial pathway. J Cell Biochem. 2004;92(6):1257-70.
Song, J. J., & Lee, Y. J. (2004). Daxx deletion mutant (amino acids 501-625)-induced apoptosis occurs through the JNK/p38-Bax-dependent mitochondrial pathway. Journal of Cellular Biochemistry, 92(6), 1257-70.
Song JJ, Lee YJ. Daxx Deletion Mutant (amino Acids 501-625)-induced Apoptosis Occurs Through the JNK/p38-Bax-dependent Mitochondrial Pathway. J Cell Biochem. 2004 Aug 15;92(6):1257-70. PubMed PMID: 15258908.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Daxx deletion mutant (amino acids 501-625)-induced apoptosis occurs through the JNK/p38-Bax-dependent mitochondrial pathway. AU - Song,Jae J, AU - Lee,Yong J, PY - 2004/7/20/pubmed PY - 2005/3/19/medline PY - 2004/7/20/entrez SP - 1257 EP - 70 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 92 IS - 6 N2 - Death-associated protein (Daxx) deletion mutant (aa 501-625) has been known to be an inducer of apoptosis. In this study, we observed that the Bax-dependent mitochondrial death signaling pathway plays an important role in Daxx501-625-induced apoptosis. Daxx fragment-induced activation of caspase-9 and -3 was mediated through the apoptosis signal-regulating kinase 1 (ASK1)-MEK-c-Jun-N-terminal kinase (JNK)/p38-Bax pathway. By overexpressing JNK-binding domain (JBD) of JIP1, a JNK-inhibitory protein, and treatment with SB203580, a specific p38 inhibitor, DU-145 cells were made resistant to Daxx501-625-induced apoptosis. Capase-3 deficiency, Bax deficiency, or overexpression of a dominant-negative caspase-9 mutant prevented apoptosis, even though the Daxx501-625 fragment still activated the ASK1-MEK-MAPK pathway. Interestingly, Daxx501-625-induced Bcl-2 interacting domain (Bid) cleavage was suppressed in the dominant-negative caspase-9 mutant cells, whereas Bim was still phosphorylated in these cells. These results suggest that cleavage of Bid occurs downstream of caspase-9 activation. In contrast, phosphorylation of Bim is upstream of caspase-9 activation. Taken together, our results suggest that Daxx501-625-induced apoptosis is mediated through the ASK1-MEK-JNK/p38-Bim-Bax-dependent caspase pathway. SN - 0730-2312 UR - https://www.unboundmedicine.com/medline/citation/15258908/Daxx_deletion_mutant__amino_acids_501_625__induced_apoptosis_occurs_through_the_JNK/p38_Bax_dependent_mitochondrial_pathway_ L2 - https://doi.org/10.1002/jcb.20155 DB - PRIME DP - Unbound Medicine ER -