PDLIM7 is a novel target of the ubiquitin ligase Nedd4-1 in skeletal muscle

2016 ◽  
Vol 473 (3) ◽  
pp. 267-276 ◽  
Author(s):  
Robert D'Cruz ◽  
Pamela J. Plant ◽  
Lesley A. Pablo ◽  
Shouzhe Lin ◽  
Joshua Chackowicz ◽  
...  

Nedd4-1 (neural precursor cell-expressed developmentally down-regulated 4-1) mediates skeletal muscle atrophy. We identify PDLIM7 as a novel Nedd4-1 substrate, binding Nedd4-1 WW domains via its PY motif and co-localizing with Nedd4-1 in myotubes. The interaction results in PDLIM7 ubiquitination and may underlie Nedd4-1-mediated muscle wasting.

2009 ◽  
Vol 419 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Pamela J. Plant ◽  
Judy Correa ◽  
Neil Goldenberg ◽  
James Bain ◽  
Jane Batt

The inositol phosphatase, MTMR4 (myotubularin-related protein 4), was identified as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4). hMTMR4 (human MTMR4) and Nedd4 co-immunoprecipitated and co-localized to late endosomes. The PY (Pro-Tyr) motif of hMTMR4 binds to WW (Trp-Trp) domains of hNedd4. MTMR4 expression was decreased in atrophying muscle, whereas Nedd4 expression was increased and hMTMR4 was ubiquitinated by hNedd4, suggesting that this novel interaction may underlie the biological process of muscle breakdown.


2005 ◽  
Vol 19 (12) ◽  
pp. 3073-3084 ◽  
Author(s):  
Vivek Bhalla ◽  
Dorothée Daidié ◽  
Hongyan Li ◽  
Alan C. Pao ◽  
Lila P. LaGrange ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Shangdan Xie ◽  
Lu Xia ◽  
Yizuo Song ◽  
Hejing Liu ◽  
Zhi-wei Wang ◽  
...  

Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) is an E3 ubiquitin ligase that has been reported to participate in multiple cellular procedures by regulating of substrate ubiquitination and subsequent protein degradation. A great amount of evidence has demonstrated that NEDD4L mainly functions as a tumor suppressor in most cancer types, while it also acts as an oncogene in a few cancers. In this review, we summarize the potential role of NEDD4L in carcinogenesis and the related underlying molecular mechanism to improve our understanding of its functions in the tumorigenesis of human malignancies. Developing clinical drugs targeting NEDD4L could be a potential therapeutic strategy for cancer therapy in the future.


2011 ◽  
Vol 6 (3) ◽  
pp. 229-254 ◽  
Author(s):  
Behnam A. Baghbaderani ◽  
Karim Mukhida ◽  
Murray Hong ◽  
Ivar Mendez ◽  
Leo A. Behie

2017 ◽  
Vol 64 (2) ◽  
pp. 287-299 ◽  
Author(s):  
Ciqing Yang ◽  
Xiaoying Li ◽  
Qiuling Li ◽  
Han Li ◽  
Liang Qiao ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiongwei Yu ◽  
Wenjun Han ◽  
Changli Wang ◽  
Daming Sui ◽  
Jinjun Bian ◽  
...  

Hemin, an inducer of heme oxygenase-1 (HO-1), can enhance the activation of HO-1. HO-1 exhibits a variety of activities, such as anti-inflammatory, antioxidative, and antiapoptotic functions. The objective of this study was to investigate the effects of hemin on sepsis-induced skeletal muscle wasting and to explore the mechanisms by which hemin exerts its effects. Cecal ligation and perforation (CLP) was performed to create a sepsis mouse model. Mice were randomly divided into four groups: control, CLP, CLP plus group, and CLP-hemin-ZnPP (a HO-1 inhibitor). The weight of the solei from the mice was measured, and histopathology was examined. Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to assess the expression levels of HO-1 and atrogin-1. Furthermore, we investigated the antioxidative effects of HO-1 by detecting malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. CLP led to dramatic skeletal muscle weakness and atrophy, but pretreatment with hemin protected mice against CLP-mediated muscle atrophy. Hemin also induced high HO-1 expression, which resulted in suppressed proinflammatory cytokine and reactive oxygen species (ROS) production. The expression of MuRF1 and atrogin-1, two ubiquitin ligases of the ubiquitin-proteasome system- (UPS-) mediated proteolysis, was also inhibited by increased HO-1 levels. Hemin-mediated increases in HO-1 expression exert protective effects on sepsis-induced skeletal muscle atrophy at least partly by inhibiting the expression of proinflammatory cytokines, UPS-mediated proteolysis, and ROS activation. Therefore, hemin might be a new treatment target against sepsis-induced skeletal muscle atrophy.


2007 ◽  
Vol 1159 ◽  
pp. 67-76 ◽  
Author(s):  
Joseph C. Lim ◽  
Adam J. Wolpaw ◽  
Maeve A. Caldwell ◽  
Stephen B. Hladky ◽  
Margery A. Barrand

Author(s):  
Behnam A. Baghbaderani ◽  
Arindom Sen ◽  
Michael S. Kallos ◽  
Leo A. Behie

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