Aberrant cytoplasmic localization of N-CoR in colorectal tumors.
We have previously shown that IKKs are aberrantly activated in colon cancer cells leading to SMRT phosphorylation and its release from the chromatin. We now show that IKKalpha phosphorylates the homologous N-CoR corepressor in serines 2345 and 2348 creating a functional 14-3-3 binding domain (RK(p)S(2348)KSP). Moreover, we have analyzed the subcellular localization of N-CoR in 43 colorectal cancer samples and we have found that aberrant cytoplasmic distribution of N-CoR is a general trait of these tumors.
Fernández-Majada
Vanessa
V
Centre Oncologia Molecular, Institut d'Investigacio Biomèdica de Bellvitge, Hospitalet, Barcelona, Spain.
Pujadas
Jaume
J
Vilardell
Felip
F
Capella
Gabriel
G
Mayo
Marty W
MW
Bigas
Anna
A
Espinosa
Lluis
L
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003106:Colon / Q000166:cytology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2; D017434:Protein Structure, Tertiary; D012007:Rectum / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism
D048948:14-3-3 Proteins; D004268:DNA-Binding Proteins; C539130:NCOR2 protein, human; D009687:Nuclear Proteins; D056985:Nuclear Receptor Co-Repressor 2; D012097:Repressor Proteins; D012694:Serine; D051550:I-kappa B Kinase