دورية أكاديمية
Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4.
| العنوان: | Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4. |
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| المؤلفون: | Bullard SA; From the Department of Internal Medicine.; Fraternal Order of Eagles Diabetes Research Center, and.; Departments of Molecular Physiology and Biophysics and.; the Iowa City Veterans Affairs Medical Center, Iowa City, Iowa 52246., Seo S; Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa 52242., Schilling B; the Buck Institute for Research on Aging, Novato, California 94945, and., Dyle MC; From the Department of Internal Medicine.; Fraternal Order of Eagles Diabetes Research Center, and.; Departments of Molecular Physiology and Biophysics and.; the Iowa City Veterans Affairs Medical Center, Iowa City, Iowa 52246.; Emmyon, Inc., Coralville, Iowa 52241., Dierdorff JM; From the Department of Internal Medicine.; Fraternal Order of Eagles Diabetes Research Center, and.; Departments of Molecular Physiology and Biophysics and.; the Iowa City Veterans Affairs Medical Center, Iowa City, Iowa 52246., Ebert SM; From the Department of Internal Medicine.; Fraternal Order of Eagles Diabetes Research Center, and.; Departments of Molecular Physiology and Biophysics and.; the Iowa City Veterans Affairs Medical Center, Iowa City, Iowa 52246.; Emmyon, Inc., Coralville, Iowa 52241., DeLau AD; From the Department of Internal Medicine.; Fraternal Order of Eagles Diabetes Research Center, and.; Departments of Molecular Physiology and Biophysics and.; the Iowa City Veterans Affairs Medical Center, Iowa City, Iowa 52246., Gibson BW; the Buck Institute for Research on Aging, Novato, California 94945, and.; the Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, California 94143., Adams CM; From the Department of Internal Medicine, christopher-adams@uiowa.edu.; Fraternal Order of Eagles Diabetes Research Center, and.; Departments of Molecular Physiology and Biophysics and.; the Iowa City Veterans Affairs Medical Center, Iowa City, Iowa 52246.; Emmyon, Inc., Coralville, Iowa 52241. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2016 Aug 19; Vol. 291 (34), pp. 17496-17509. Date of Electronic Publication: 2016 Jun 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Cell Cycle Proteins/*metabolism , MAP Kinase Kinase Kinase 4/*metabolism , Multiprotein Complexes/*metabolism , Muscle Fibers, Skeletal/*metabolism , Muscular Atrophy/*metabolism , Nuclear Proteins/*metabolism, Animals ; Cell Cycle Proteins/genetics ; MAP Kinase Kinase Kinase 4/genetics ; Mice ; Multiprotein Complexes/genetics ; Muscle Fibers, Skeletal/pathology ; Muscular Atrophy/genetics ; Muscular Atrophy/pathology ; Nuclear Proteins/genetics |
| مستخلص: | Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.) |
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| معلومات مُعتمدة: | I01 BX000976 United States BX BLRD VA; S10 OD016281 United States OD NIH HHS; R01 EY022616 United States EY NEI NIH HHS; I01 RX001477 United States RX RRD VA; R01 AR059115 United States AR NIAMS NIH HHS |
| فهرسة مساهمة: | Keywords: Gadd45a; MEKK4; aging; mass spectrometry (MS); muscle; muscle atrophy; skeletal muscle; skeletal muscle metabolism |
| المشرفين على المادة: | 0 (Cell Cycle Proteins) 0 (Gadd45a protein, mouse) 0 (Multiprotein Complexes) 0 (Nuclear Proteins) EC 2.7.11.25 (MAP Kinase Kinase Kinase 4) EC 2.7.11.25 (Map3k4 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20160701 Date Completed: 20170512 Latest Revision: 20210205 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5016147 |
| DOI: | 10.1074/jbc.M116.740308 |
| PMID: | 27358404 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1083-351X |
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| DOI: | 10.1074/jbc.M116.740308 |