MuRF1 Partners With TRIM72 to Impair Insulin Signaling in Skeletal Muscle Cells

Musa, I ORCID: 0000-0003-2390-8241, Seabright, AP, Barlow, J and Nishimura, Y ORCID: 0000-0001-8225-7675 (2025) MuRF1 Partners With TRIM72 to Impair Insulin Signaling in Skeletal Muscle Cells. The FASEB Journal, 39 (19). ISSN 0892-6638

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Abstract

Muscle RING-finger protein 1 (MuRF1, gene name: TRIM63) is well known as a critical molecular regulator in skeletal muscle atrophy. Despite the identification of several substrates and interaction partners for MuRF1, the precise molecular mechanisms by which MuRF1 causes skeletal muscle atrophy remain unclear. To gain further insight into the underlying mechanism of skeletal muscle atrophy, we applied targeted biochemical approaches and identified tripartite motif-containing protein 72 (TRIM72) as a novel MuRF1-interacting protein. Subsequent analysis using MuRF1 knockout and rescue experiments showed that TRIM72 protein abundance is dependent on the presence of MuRF1 protein. Furthermore, TRIM72 protein level was increased by dexamethasone treatment in C2C12 myotubes, alongside increased MuRF1 protein level. Dexamethasone decreases IRS1/Akt signaling and glucose uptake specifically in wild type myotubes, but not in MuRF1 KO myotubes. Further analysis showed that overexpression of TRIM72 impairs IRS1/Akt signaling without the presence of MuRF1, indicating that MuRF1 induces a negative impact on insulin signaling through a plausible cooperation with TRIM72. Our findings provide novel non-degradative molecular roles of MuRF1 that link together skeletal muscle atrophy and impaired insulin sensitivity.

Item Type:	Article
Uncontrolled Keywords:	0601 Biochemistry and Cell Biology; 0606 Physiology; 1116 Medical Physiology; Biochemistry & Molecular Biology; 3101 Biochemistry and cell biology; 3208 Medical physiology
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport and Exercise Sciences
Publisher:	Wiley
Date of acceptance:	18 September 2025
Date of first compliant Open Access:	3 October 2025
Date Deposited:	03 Oct 2025 10:41
Last Modified:	03 Oct 2025 10:45
DOI or ID number:	10.1096/fj.202502066rr
URI:	https://researchonline.ljmu.ac.uk/id/eprint/27256

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