Title |
Senescence-inducing stress promotes proteolysis of phosphoglycerate mutase via ubiquitin ligase Mdm2
|
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Published in |
Journal of Cell Biology, February 2014
|
DOI | 10.1083/jcb.201306149 |
Pubmed ID | |
Authors |
Takumi Mikawa, Takeshi Maruyama, Koji Okamoto, Hitoshi Nakagama, Matilde E. Lleonart, Takeshi Tsusaka, Kousuke Hori, Itsuo Murakami, Taisuke Izumi, Akifumi Takaori-Kondo, Masayuki Yokode, Gordon Peters, David Beach, Hiroshi Kondoh |
Abstract |
Despite the well-documented clinical significance of the Warburg effect, it remains unclear how the aggressive glycolytic rates of tumor cells might contribute to other hallmarks of cancer, such as bypass of senescence. Here, we report that, during oncogene- or DNA damage-induced senescence, Pak1-mediated phosphorylation of phosphoglycerate mutase (PGAM) predisposes the glycolytic enzyme to ubiquitin-mediated degradation. We identify Mdm2 as a direct binding partner and ubiquitin ligase for PGAM in cultured cells and in vitro. Mutations in PGAM and Mdm2 that abrogate ubiquitination of PGAM restored the proliferative potential of primary cells under stress conditions and promoted neoplastic transformation. We propose that Mdm2, a downstream effector of p53, attenuates the Warburg effect via ubiquitination and degradation of PGAM. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 3 | 5% |
United States | 1 | 2% |
Unknown | 51 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 12 | 22% |
Researcher | 6 | 11% |
Student > Doctoral Student | 5 | 9% |
Professor | 4 | 7% |
Professor > Associate Professor | 4 | 7% |
Other | 11 | 20% |
Unknown | 13 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 20 | 36% |
Biochemistry, Genetics and Molecular Biology | 11 | 20% |
Medicine and Dentistry | 6 | 11% |
Chemical Engineering | 1 | 2% |
Nursing and Health Professions | 1 | 2% |
Other | 3 | 5% |
Unknown | 13 | 24% |