Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation.
Journal
Oncogenesis
ISSN: 2157-9024
Titre abrégé: Oncogenesis
Pays: United States
ID NLM: 101580004
Informations de publication
Date de publication:
28 Sep 2020
28 Sep 2020
Historique:
received:
27
05
2020
accepted:
15
09
2020
revised:
30
08
2020
entrez:
29
9
2020
pubmed:
30
9
2020
medline:
30
9
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32989218
doi: 10.1038/s41389-020-00271-1
pii: 10.1038/s41389-020-00271-1
pmc: PMC7522278
doi:
Types de publication
Journal Article
Langues
eng
Pagination
85Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : CA210929
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : CA193124
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : CA216437
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : CA216911
Organisme : Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)
ID : RP160667
Organisme : NCI NIH HHS
ID : R01 CA216437
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216911
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA210929
Pays : United States
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