Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor

Oncoproteins and tumor suppressors antagonistically converge on critical nodes governing neoplastic growth, invasion, and metastasis. We discovered that phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific serine or threonine residues creates binding sites for the COP1 tumor...

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Vydané v:Cancer cell Ročník 26; číslo 2; s. 222
Hlavní autori: Lu, Gang, Zhang, Qing, Huang, Ying, Song, Jiaxi, Tomaino, Ross, Ehrenberger, Tobias, Lim, Elgene, Liu, Wenbin, Bronson, Roderick T, Bowden, Michaela, Brock, Jane, Krop, Ian E, Dillon, Deborah A, Gygi, Steven P, Mills, Gordon B, Richardson, Andrea L, Signoretti, Sabina, Yaffe, Michael B, Kaelin, Jr, William G
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 11.08.2014
Predmet:
Amino Acid Sequence
Animals
Binding Sites
Female
HCT116 Cells
HEK293 Cells
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Molecular Sequence Data
Neoplasm Transplantation
Phosphorylation
Protein Binding
Proto-Oncogene Protein c-ets-1 - metabolism
Proto-Oncogene Protein c-ets-2 - metabolism
src-Family Kinases - metabolism
Triple Negative Breast Neoplasms - enzymology
Triple Negative Breast Neoplasms - pathology
Tumor Burden
Ubiquitin-Protein Ligases - chemistry
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
ISSN:1878-3686, 1878-3686
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Shrnutí:Oncoproteins and tumor suppressors antagonistically converge on critical nodes governing neoplastic growth, invasion, and metastasis. We discovered that phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific serine or threonine residues creates binding sites for the COP1 tumor suppressor protein, which is an ubiquitin ligase component, leading to their destruction. In the case of ETS1, however, phosphorylation of a neighboring tyrosine residue by Src family kinases disrupts COP1 binding, thereby stabilizing ETS1. Src-dependent accumulation of ETS1 in breast cancer cells promotes anchorage-independent growth in vitro and tumor growth in vivo. These findings expand the list of potential COP1 substrates to include proteins whose COP1-binding sites are subject to regulatory phosphorylation and provide insights into transformation by Src family kinases.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1878-3686
1878-3686
DOI:10.1016/j.ccr.2014.06.026