In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 14, No. 669 ( 2022-11-02)
Abstract:
During heart failure, transcription factors involved in cardiomyocyte survival are repressed. Here, Lorenzana-Carrillo et al. studied the role of pyruvate kinase M2 (PKM2), a glycolytic enzyme, in regulating the transcription factors GATA4/6 and P53. Mice lacking PKM2 in cardiomyocytes had decreased GATA4/6 but increased P53 and developed dilated cardiomyopathy. In adult cardiomyocytes, they observed direct interaction between nuclear PKM2 and the transcription factors, where PKM2 prevented cleavage and degradation of GATA4/6 but promoted P53 degradation. The E3 ubiquitin ligase TRIM35 was found to degrade nuclear PKM2, resulting in cardiac dysfunction when overexpressed in cardiomyocytes in mice, and TRIM35 was up-regulated in human heart failure tissue samples. Results help identify the role of PKM2 in cardiomyocyte survival in heart failure.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.abm3565
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022
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