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Updated: Jul 13, 2026
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
Aberrant cytoplasmic localization of N-CoR in colorectal tumors
Vanessa Fernández-Majada1, Jaume Pujadas, Felip Vilardell
1Centre Oncologia Molecular, Institut d'Investigacio Biomèdica de Bellvitge, Hospitalet, Barcelona, Spain.
Abstract:
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.
Insights
Inhibitor of kappaB kinases (IKKs) activate in colon cancer, causing Nuclear Receptor corepressor (N-CoR) to shift to the cytoplasm. This aberrant N-CoR localization is a common feature in colorectal tumors.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Aberrant activation of Inhibitor of kappaB kinases (IKKs) is observed in colon cancer cells.
- This activation leads to SMRT phosphorylation and subsequent release from chromatin.
Purpose of the Study:
- To investigate the phosphorylation of Nuclear Receptor corepressor (N-CoR) by IKKalpha.
- To analyze the subcellular localization of N-CoR in colorectal cancer samples.
Main Methods:
- Biochemical assays to determine IKKalpha-mediated phosphorylation sites on N-CoR.
- Analysis of N-CoR subcellular distribution in 43 human colorectal cancer tissues.
Main Results:
- IKKalpha phosphorylates N-CoR at serines 2345 and 2348, creating a 14-3-3 binding domain.
- Aberrant cytoplasmic localization of N-CoR was identified as a general characteristic in colorectal tumors.
Conclusions:
- IKKalpha-mediated phosphorylation of N-CoR contributes to its altered subcellular distribution in colon cancer.
- The cytoplasmic mislocalization of N-CoR is a prevalent feature in colorectal cancer, suggesting a role in tumorigenesis.
