B cell lymphoma 2 (Bcl-2) residues essential for Bcl-2's apoptosis-inducing interaction with Nur77/Nor-1 orphan steroid receptors.
In: The Journal of biological chemistry, Jg. 293 (2018-03-30), Heft 13, S. 4724-4734
academicJournal
Zugriff:
Apoptosis is mediated through the extrinsic or intrinsic pathway. Key regulators of the intrinsic apoptotic pathway are the family of B cell lymphoma 2 (Bcl-2) proteins. The activity of the prototypical Bcl-2 protein is usually considered antiapoptotic. However, under some conditions, Bcl-2 associates with the orphan nuclear hormone receptors Nur77 and Nor-1, converting Bcl-2 into a proapoptotic molecule. Expression of Nur77 and Nor-1 is induced by a variety of signals, including those leading to apoptosis. Translocation of Nur77/Nor-1 to mitochondria results in their association with Bcl-2, exposing the Bcl-2 homology (BH) 3 domain and causing apoptosis. However, the molecular details of this interaction are incompletely understood. Here, through extensive Bcl-2 mutagenesis and functional assays, we identified residues within Bcl-2 that are essential for its interaction with Nur77/Nor-1. Although an initial report has suggested that an unstructured loop region between the Bcl-2 BH4 and BH3 domains is required for Bcl-2's interaction with Nur77/Nor-1, we found that it is dispensable for this interaction. Instead, we found important interacting residues at the BH4 domain and crucial interacting residues between the BH1 and BH2 domains. Bcl-2 alanine mutants at this region could no longer interact with Nur77/Nor-1 and could not initiate Nur77/Bcl-2-mediated cell death. However, they still retained their anti-apoptotic capability in two different death assays. These results establish crucial residues in Bcl-2 required for Nur77/Nor-1-mediated apoptosis and point to potential new strategies for manipulating Bcl-2 function.
(© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)
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B cell lymphoma 2 (Bcl-2) residues essential for Bcl-2's apoptosis-inducing interaction with Nur77/Nor-1 orphan steroid receptors.
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Autor/in / Beteiligte Person: | Banta, KL ; Wang, X ; Das, P ; Winoto, A |
Zeitschrift: | The Journal of biological chemistry, Jg. 293 (2018-03-30), Heft 13, S. 4724-4734 |
Veröffentlichung: | 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology ; <i>Original Publication</i>: Baltimore, MD : American Society for Biochemistry and Molecular Biology, 2018 |
Medientyp: | academicJournal |
ISSN: | 1083-351X (electronic) |
DOI: | 10.1074/jbc.RA117.001101 |
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