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Identification of methyllysine peptides binding to chromobox protein homolog 6 chromodomain in the human proteome.

ABSTRACT: Methylation is one of the important post-translational modifications that play critical roles in regulating protein functions. Proteomic identification of this post-translational modification and understanding how it affects protein activity remain great challenges. We tackled this problem from the aspect of methylation mediating protein-protein interaction. Using the chromodomain of human chromobox protein homolog 6 as a model system, we developed a systematic approach that integrates structure modeling, bioinformatics analysis, and peptide microarray experiments to identify lysine residues that are methylated and recognized by the chromodomain in the human proteome. Given the important role of chromobox protein homolog 6 as a reader of histone modifications, it was interesting to find that the majority of its interacting partners identified via this approach function in chromatin remodeling and transcriptional regulation. Our study not only illustrates a novel angle for identifying methyllysines on a proteome-wide scale and elucidating their potential roles in regulating protein function, but also suggests possible strategies for engineering the chromodomain-peptide interface to enhance the recognition of and manipulate the signal transduction mediated by such interactions.

SUBMITTER: Li N

PROVIDER: S-EPMC3790288 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Identification of methyllysine peptides binding to chromobox protein homolog 6 chromodomain in the human proteome.

Li Nan N Stein Richard S L RS He Wei W Komives Elizabeth E Wang Wei W

Molecular & cellular proteomics : MCP 20130710 10

Methylation is one of the important post-translational modifications that play critical roles in regulating protein functions. Proteomic identification of this post-translational modification and understanding how it affects protein activity remain great challenges. We tackled this problem from the aspect of methylation mediating protein-protein interaction. Using the chromodomain of human chromobox protein homolog 6 as a model system, we developed a systematic approach that integrates structure ...[more]

PMID: 23842000

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Project description:Cholangiocarcinoma is a highly malignant form of gastrointestinal cancer with an unfavorable prognosis. The novel oncogene chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) has been confirmed to serve a vital role in numerous types of cancer, including liver cancer. Mismatch repair (MMR) is a common DNA repair process that contributes to the preservation of the integrity and stability of genetic substances. Human mutL homolog 1 gene (hMLH1) is an important MMR protein family member. The present study aimed to evaluate the pathological and clinical features of cholangiocarcinoma, and to investigate the clinical significance of CHD1L and hMLH1 expression in cholangiocarcinoma. A total of 108 samples from cholangiocarcinoma tumor tissues and 60 samples from normal bile duct tissue were obtained from patients admitted to The Second Affiliated Hospital of Nanchang University between May 2005 and May 2014. All cholangiocarcinoma cases were pathologically confirmed. The expression of CHD1L and hMLH1 was examined by immunohistochemistry analysis. The expression of CHD1L in cholangiocarcinoma (94.44%) was significantly higher than in normal bile duct tissues (40.00%). CHD1L expression was associated with gallstone history, serum carbohydrate antigen 19-9 (CA19-9) level and Tumor-Node-Metastasis (TNM) stage (P<0.05). hMLH1 expression in cholangiocarcinoma (77.78%) was significantly lower than in normal bile duct tissues (96.67%), and was associated with gender, age, serum CA19-9 level, the presence of hepatitis B virus surface antigen, TNM stage and tumor diameter (P<0.05). Kaplan-Meier survival curve analysis indicated that the 3-year accumulative survival rates for CHD1L-positive and -negative patients differed significantly (P<0.05; 17.90 and 83.33%, respectively). There was no statistically significant difference (P>0.05) between the 3-year accumulate survival rates for hMLH1-positive and -negative patients (38.90 and 33.30%, respectively). High CHD1L expression and low hMLH1 expression levels were observed in patients with cholangiocarcinoma, and their abnormal expression patterns were associated with the progression of malignancy and an unfavorable disease prognosis. Therefore, CHD1L and hMLH1 may be potential prognostic biomarkers for cholangiocarcinoma.

Dataset Information

Identification of methyllysine peptides binding to chromobox protein homolog 6 chromodomain in the human proteome.

Publications

Identification of methyllysine peptides binding to chromobox protein homolog 6 chromodomain in the human proteome.

Similar Datasets

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