A novel gene IC53 stimulates ECV304 cell proliferation and is upregulated in failing heart

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Abstract

C53, cloned from rat brain cDNA library, can bind to p35, the precursor of activator of Cdk5. A novel gene with 84% homolog to C53, named IC53, was cloned from our 5300 EST database of human aorta cDNA library (GenBank Accession No. AF110322). Computational analysis showed that IC53 cDNA is 2538 bp long, encoding 419 amino acids, mapped to chromosome 17q21.31 with 12 exons, ubiquitously expressed in 12 tested normal tissues and 8 tumor cell lines from MTN membranes and vascular endothelial cells by Northern blot and in situ hybridization, and upregulated in the rat models of subacute heart failure and chronic ischemic heart failure by left coronary ligation. Stable transfection of IC53 stimulates ECV304 cell proliferation by 2.1-fold compared to cells with empty vector (P<0.05). The results support that IC53 is a novel gene, mainly expressed in vascular endothelial cells and mediates cell proliferation.

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Materials and methods

Computational characterization of IC53. Computational characterization of IC53 was performed as follows: homologous comparisons between species and chromosome localization of IC53 through BLAST, the database “nr” and “Human Genome”, at http://www.ncbi.nlm.nih.gov/BLAST/, prediction of theoretical molecular weight and isoelectric point at http://www.expasy.ch/tools/protparam.html, searching membrane-spanning motif at http://www.cbs.dtu.dk/services/TMHMM-1.0/, characterizing pattern and profiles

Cloning and molecular features of IC53

We isolated a full-length IC53 cDNA (2538 bp) from human aorta cDNA library, encoding a putative protein of 419 amino acids (Fig. 1A), mapped to chromosome 17q21.31 with 12 exons and a theoretical isoelectric point of 4.56, and calculated molecular mass of 46.3 kDa. Database searches indicated that the predicted protein is 84% identity throughout human C53 (Figs. 1B and C). No known membrane-spanning motif and putative signal peptide sequence were detected, suggesting an intracellular protein.

Discussion

In this study, we have identified and characterized a previously uncharacterized gene termed IC53 that possesses structural similarity to C53, a Cdk5 binding protein precursor with unknown function, but IC53 has ability to stimulate endothelial cell to grow. IC53 mRNA is ubiquitously expressed in all tested tissues and tumor cell lines with different levels and over-expressed in failing heart in animal models. During heart failure, especially ischemic heart failure, cardiac myocytes need more

Acknowledgements

This work was supported by China National 863 High-tech Grants Z19-02-02-01 and 102100405 and National P73 Basic Research Grant (to Dr. Rutai Hui).

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Jingzhou Chen is a PhD candidate in Sino-German Laboratory, Cardiovascular Institute, Peking Union Medical College, Beijing, China.

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