The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
MCL-1S, a Splicing Variant of the Antiapoptotic BCL-2 Family Member MCL-1, Encodes a Proapoptotic Protein Possessing Only the BH3 Domain
Open accessAbstract
MCL-1 (myeloid cell leukemia-1) is an antiapoptotic BCL-2 family protein discovered as an early induction gene during myeloblastic leukemia cell differentiation. This survival protein has the BCL-2 homology (BH) domains 1, 2, and 3 and a C-terminal transmembrane region. We identified a short splicing variant of the MCL-1 mRNA in the human placenta encoding a protein, termed MCL-1 short (MCL-1S), with an altered C terminus as compared with the full-length MCL-1 long (MCL-1L), leading to the loss of BH1, BH2, and the transmembrane domains. Analysis of the human MCL-1 gene indicated that MCL-1S results from the splicing out of exon 2 during mRNA processing. MCL-1S, unlike MCL-1L, does not interact with diverse proapoptotic BCL-2-related proteins in the yeast two-hybrid system. In contrast, MCL-1S dimerizes with MCL-1L in the yeast assay and coprecipitates with MCL-1L in transfected mammalian cells. Overexpression of MCL-1S induces apoptosis in transfected Chinese hamster ovary cells, and the MCL-1S action was antagonized by the antiapoptotic MCL-1L. Thus, the naturally occurring MCL-1S variant represents a new proapoptotic BH3 domain-only protein capable of dimerizing with the antiapoptotic MCL-1L. The fate of MCL-1-expressing cells could be regulated through alternative splicing mechanisms and interactions of the resulting anti- and proapoptotic gene products.
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Cited by
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Notch Promotes Radioresistance of Glioma Stem Cells
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The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer
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Metadata
- Authors
- Bae, J., Leo, C. P., Hsu, S. Y., & Hsueh, A. J. W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-08
- Volume
- 275
- Issue
- 33
- Pages
- 25255-25261
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2010336934
- Cited by
- 289
- References
- 52
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Bae, J., Leo, C. P., Hsu, S. Y., & Hsueh, A. J. W. (2000). MCL-1S, a Splicing Variant of the Antiapoptotic BCL-2 Family Member MCL-1, Encodes a Proapoptotic Protein Possessing Only the BH3 Domain. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m909826199
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