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- Title
Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation.
- Authors
Wang, Chao; Chen, Zhen; Nie, Litong; Tang, Mengfan; Feng, Xu; Su, Dan; Zhang, Huimin; Xiong, Yun; Park, Jeong-Min; Chen, Junjie
- Abstract
The ERK1/2 pathway is one of the most commonly dysregulated pathways in human cancers and controls many vital cellular processes. Although many ERK1/2 kinase substrates have been identified, the diversity of ERK1/2 mediated processes suggests the existence of additional targets. Here, we identified Deoxyhypusine synthase (DHPS), an essential hypusination enzyme regulating protein translation, as a major and direct-binding protein of ERK1/2. Further experiments showed that ERK1/2 phosphorylate DHPS at Ser-233 site. The Ser-233 phosphorylation of DHPS by ERK1/2 is important for its function in cell proliferation. Moreover, we found that higher DHPS expression correlated with poor prognosis in lung adenocarcinoma and increased resistance to inhibitors of the ERK1/2 pathway. In summary, our results suggest that ERK1/2-mediated DHPS phosphorylation is an important mechanism that underlies protein translation and that DHPS expression is a potent biomarker of response to therapies targeting ERK1/2-pathway.
- Publication
Oncogenesis, 2020, Vol 9, Issue 9, p1
- ISSN
2157-9024
- Publication type
Article
- DOI
10.1038/s41389-020-00271-1