Skip to main content
Journal cover image

Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I.

Publication ,  Journal Article
Kedar, V; McDonough, H; Arya, R; Li, H-H; Rockman, HA; Patterson, C
Published in: Proc Natl Acad Sci U S A
December 28, 2004

Muscle-specific RING finger protein 1 (MuRF1) is a sarcomere-associated protein that is restricted to cardiac and skeletal muscle. In skeletal muscle, MuRF1 is up-regulated by conditions that provoke atrophy, but its function in the heart is not known. The presence of a RING finger in MuRF1 raises the possibility that it is a component of the ubiquitin-proteasome system of protein degradation. We performed a yeast two-hybrid screen to search for interaction partners of MuRF1 in the heart that might be targets of its putative ubiquitin ligase activity. This screen identified troponin I as a MuRF1 partner protein. MuRF1 and troponin I were found to associate both in vitro and in vivo in cultured cardiomyocytes. MuRF1 reduced steady-state troponin I levels when coexpressed in COS-7 cells and increased degradation of endogenous troponin I protein in cardiomyocytes. The degradation of troponin I in cardiomyocytes was associated with the accumulation of ubiquitylated intermediates of troponin I and was proteasome-dependent. In vitro, MuRF1 functioned as a ubiquitin ligase to catalyze ubiquitylation of troponin I through a RING finger-dependent mechanism. In isolated cardiomyocytes, MuRF1 reduced indices of contractility. In cardiomyocytes, these processes may determine the balance between hypertrophic and antihypertrophic signals and the regulation of myocyte contractile responses in the setting of heart failure.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

December 28, 2004

Volume

101

Issue

52

Start / End Page

18135 / 18140

Location

United States

Related Subject Headings

  • Up-Regulation
  • Ubiquitin-Protein Ligases
  • Ubiquitin
  • Two-Hybrid System Techniques
  • Troponin I
  • Tripartite Motif Proteins
  • Time Factors
  • Rats
  • Protein Structure, Tertiary
  • Protein Binding
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kedar, V., McDonough, H., Arya, R., Li, H.-H., Rockman, H. A., & Patterson, C. (2004). Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I. Proc Natl Acad Sci U S A, 101(52), 18135–18140. https://doi.org/10.1073/pnas.0404341102
Kedar, Vishram, Holly McDonough, Ranjana Arya, Hui-Hua Li, Howard A. Rockman, and Cam Patterson. “Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I.Proc Natl Acad Sci U S A 101, no. 52 (December 28, 2004): 18135–40. https://doi.org/10.1073/pnas.0404341102.
Kedar V, McDonough H, Arya R, Li H-H, Rockman HA, Patterson C. Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18135–40.
Kedar, Vishram, et al. “Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I.Proc Natl Acad Sci U S A, vol. 101, no. 52, Dec. 2004, pp. 18135–40. Pubmed, doi:10.1073/pnas.0404341102.
Kedar V, McDonough H, Arya R, Li H-H, Rockman HA, Patterson C. Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18135–18140.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

December 28, 2004

Volume

101

Issue

52

Start / End Page

18135 / 18140

Location

United States

Related Subject Headings

  • Up-Regulation
  • Ubiquitin-Protein Ligases
  • Ubiquitin
  • Two-Hybrid System Techniques
  • Troponin I
  • Tripartite Motif Proteins
  • Time Factors
  • Rats
  • Protein Structure, Tertiary
  • Protein Binding