Publication Date:
2008-02-22
Description:
Cytokines affect a variety of cellular functions, including regulation of cell numbers by suppression of programmed cell death. Suppression of apoptosis requires receptor signalling through the activation of Janus kinases and the subsequent regulation of members of the B-cell lymphoma 2 (Bcl-2) family. Here we demonstrate that a Bcl-2-family-related protein, Hax1, is required to suppress apoptosis in lymphocytes and neurons. Suppression requires the interaction of Hax1 with the mitochondrial proteases Parl (presenilin-associated, rhomboid-like) and HtrA2 (high-temperature-regulated A2, also known as Omi). These interactions allow Hax1 to present HtrA2 to Parl, and thereby facilitates the processing of HtrA2 to the active protease localized in the mitochondrial intermembrane space. In mouse lymphocytes, the presence of processed HtrA2 prevents the accumulation of mitochondrial-outer-membrane-associated activated Bax, an event that initiates apoptosis. Together, the results identify a previously unknown sequence of interactions involving a Bcl-2-family-related protein and mitochondrial proteases in the ability to resist the induction of apoptosis when cytokines are limiting.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chao, Jyh-Rong -- Parganas, Evan -- Boyd, Kelli -- Hong, Cheol Yi -- Opferman, Joseph T -- Ihle, James N -- England -- Nature. 2008 Mar 6;452(7183):98-102. doi: 10.1038/nature06604. Epub 2008 Feb 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18288109" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Apoptosis
;
Cell Survival
;
Genes, Lethal
;
Lymphocytes/cytology/metabolism
;
Metalloproteases/deficiency/*metabolism
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Mitochondrial Proteins/chemistry/deficiency/*metabolism
;
Neurons/cytology/metabolism
;
Protein Binding
;
*Protein Processing, Post-Translational
;
Proteins/genetics/*metabolism
;
Serine Endopeptidases/chemistry/*metabolism
;
bcl-2-Associated X Protein/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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