The alternative splice variant of DAPK-1, s-DAPK-1, induces proteasome-independent DAPK-1 destabilization
| العنوان: | The alternative splice variant of DAPK-1, s-DAPK-1, induces proteasome-independent DAPK-1 destabilization |
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| المؤلفون: | Suresh Pathuri, Ben Harrison, Eliana Amin, Yao Lin, Ted R. Hupp, Craig Stevens |
| المصدر: | Molecular and Cellular Biochemistry. 328:101-107 |
| بيانات النشر: | Springer Science and Business Media LLC, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Proteasome Endopeptidase Complex, Vesicle-associated membrane protein 8, Clinical Biochemistry, Biology, Protein degradation, Cell Line, MAP2K7, Humans, Protein Isoforms, ASK1, c-Raf, Protein kinase A, Molecular Biology, Protein Stability, Cyclin-dependent kinase 2, Cell Biology, General Medicine, Autophagy-related protein 13, Ankyrin Repeat, Cell biology, Alternative Splicing, Death-Associated Protein Kinases, Biochemistry, Calcium-Calmodulin-Dependent Protein Kinases, biology.protein, Apoptosis Regulatory Proteins, Half-Life |
| الوصف: | Death-associated protein kinase 1 (DAPK-1) is a Ca(2+)/CaM-regulated kinase involved in multiple cellular signalling pathways that trigger cell survival, apoptosis, and autophagy. An alternatively spliced product expressed from the dapk1 locus, named s-DAPK-1, does not contain the kinase domain but has part of the DAPK-1 ankyrin-repeat and a novel polypeptide tail extension which is processed proteolytically in vivo. Cleavage of this polypeptide tail from s-DAPK-1 can regulate the ability of the protein to mimic one of the biological functions of DAPK-1 in promoting membrane blebbing. The full-length DAPK-1 protein is a relatively long-lived protein whose half-life is regulated by stress-activated signals from TNFR1 or HSP90 that can promote DAPK-1 protein degradation. Transfection of s-DAPK-1 into cells can also have a direct effect on DAPK-1 protein itself by promoting DAPK-1 de-stabilization. This effect does not require the novel polypeptide tail-extension of s-DAPK-1, as the core ankyrin-repeat containing region of s-DAPK-1 is sufficient to promote DAPK-1 protein de-stabilization. Conversely, the minimal domain on full-length DAPK-1 that responds to the effect of s-DAPK-1 is not the ankyrin-repeat domain but the core kinase domain of DAPK-1. The de-stabilization of DAPK-1 by s-DAPK-1 is not dependent upon the proteasome. However, s-DAPK-1 itself is a very short-lived protein which is regulated by a proteasomal-dependent pathway. Together, these data identify a novel function of s-DAPK-1 in controlling the half-life of DAPK-1 protein itself and indicate that the degradation of each gene product is controlled by two distinct degradation pathways. |
| تدمد: | 1573-4919 0300-8177 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78b58a198c616f4afb448ea935b4fe26Test https://doi.org/10.1007/s11010-009-0079-4Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....78b58a198c616f4afb448ea935b4fe26 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15734919 03008177 |
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