E3 Ubiquitin Ligase, WWP1, Interacts with AMPK alpha 2 and Down-regulates Its Expression in Skeletal Muscle C2C12 Cells
- Authors
- Lee, Jung Ok; Lee, Soo Kyung; Kim, Nami; Kim, Ji Hae; You, Ga Young; Moon, Ji Wook; Jie, Sha; Kim, Su Jin; Lee, Yong Woo; Kang, Ho Jin; Lim, Yongchul; Park, Sun Hwa; Kim, Hyeon Soo
- Issue Date
- 15-2월-2013
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.288, no.7, pp.4673 - 4680
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 288
- Number
- 7
- Start Page
- 4673
- End Page
- 4680
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/103953
- DOI
- 10.1074/jbc.M112.406009
- ISSN
- 0021-9258
- Abstract
- It is known that the activity of AMP-activated protein kinase (AMPK alpha 2) was depressed under high glucose conditions. However, whether protein expression of AMPK alpha 2 is also down-regulated or not remains unclear. In this study, we showed that the expression of AMPK alpha 2 was down-regulated in cells cultured under high glucose conditions. Treatment of proteasome inhibitor, MG132, blocked high glucose-induced AMPK alpha 2 downregulation. Endogenous AMPK alpha 2 ubiquitination was detected by immunoprecipitation of AMPK alpha 2 followed by immunoblotting detection of ubiquitin. The yeast-two hybrid (YTH) approach identified WWP1, an E3 ubiquitin ligase, as the AMPK alpha 2-interacting protein in skeletal muscle cells. Interaction between AMPK alpha 2 and WWP1 was validated by co-immunoprecipitation. Knockdown of WWP1 blocked high glucose-induced AMPK alpha 2 down-regulation. The overexpression of WWP1 down-regulated AMPK alpha 2. In addition, the expression of WWP1 is increased under high glucose culture conditions in both mRNA and protein levels. The level of AMPK alpha 2 was downregulated in the quadriceps muscle of diabetic animal model db/db mice. Expression of WWP1 blocked metformin-induced glucose uptake. Taken together, our results demonstrated that WWP1 down-regulated AMPK alpha 2 under high glucose culture conditions via the ubiquitin-proteasome pathway.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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