Identification and characterization of a novel gene, c1orf109, encoding a CK2 substrate that is involved in cancer cell proliferation

Journal of Biomedical Science

Yu Li¹  Yao Zhang²  Lei Yue²  You-peng Qu²  Yang Yu³  Jie He¹  Hua-dong Jiang¹  Hong-xia Zheng¹  Shan-shan Liu¹ 

[1] Department of Life Science and Engineering, Harbin Institute of Technology (HIT), Harbin, 150001, People’s Republic of China;Bio-X Center, The Academy of Fundamental and Interdisciplinary Science, Harbin Institute of Technology, Harbin, 150080, People’s Republic of China;Laboratory of Medical Genetics, Harbin Medical University, Harbin, 150001, People’s Republic of China

关键词: Proliferation;    c1orf109;    CK2 kinase;    Transcription;    Promoter;   

Others  :  825064
DOI  :  10.1186/1423-0127-19-49

 received in 2011-11-14, accepted in 2012-05-01,  发布年份 2012

【 摘 要 】

Background

In the present study we identified a novel gene, Homo Sapiens Chromosome 1 ORF109 (c1orf109, GenBank ID: NM_017850.1), which encodes a substrate of CK2. We analyzed the regulation mode of the gene, the expression pattern and subcellular localization of the predicted protein in the cell, and its role involving in cell proliferation and cell cycle control.

Methods

Dual-luciferase reporter assay, chromatin immunoprecipitation and EMSA were used to analysis the basal transcriptional requirements of the predicted promoter regions. C1ORF109 expression was assessed by western blot analysis. The subcellular localization of C1ORF109 was detected by immunofluorescence and immune colloidal gold technique. Cell proliferation was evaluated using MTT assay and colony-forming assay.

Results

We found that two cis-acting elements within the crucial region of the c1orf109 promoter, one TATA box and one CAAT box, are required for maximal transcription of the c1orf109 gene. The 5′ flanking region of the c1orf109 gene could bind specific transcription factors and Sp1 may be one of them. Employing western blot analysis, we detected upregulated expression of c1orf109 in multiple cancer cell lines. The protein C1ORF109 was mainly located in the nucleus and cytoplasm. Moreover, we also found that C1ORF109 was a phosphoprotein in vivo and could be phosphorylated by the protein kinase CK2 in vitro. Exogenous expression of C1ORF109 in breast cancer Hs578T cells induced an increase in colony number and cell proliferation. A concomitant rise in levels of PCNA (proliferating cell nuclear antigen) and cyclinD1 expression was observed. Meanwhile, knockdown of c1orf109 by siRNA in breast cancer MDA-MB-231 cells confirmed the role of c1orf109 in proliferation.

Conclusions

Taken together, our findings suggest that C1ORF109 may be the downstream target of protein kinase CK2 and involved in the regulation of cancer cell proliferation.

【 授权许可】

   
2012 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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