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Characterization of a novel human CDK5 splicing variant that inhibits Wnt/β-catenin signaling

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Abstract

The cyclin-dependent kinases (CDKs) are a family of serine/threonine kinases, playing an essential role in regulating cell-cycle progression. In our present work, human CDK5 and a novel CDK5 splicing variant, named as CDK5-SV, were cloned from the cDNA library of human testis. CDK5-SV lacking the exon 7 of CDK5 encodes a protein of 260 amino acids. Through RT-PCR analysis in different human tissues, CDK5-SV was found to be expressed in testis, skeletal muscle, colon, bone marrow and ovary, while CDK5 was ubiquitously expressed. Immunofluorescence experiment in HeLa cells showed that the subcellular localizations of CDK5-SV and CDK5 were totally different. CDK5 mainly located in the cytoplasm, while CDK5-SV accumulated in nucleus. Reporter gene assay showed that when co-transfected with β-catenin, CDK5 and CDK5-SV could both strongly inhibit the Wnt/β-catenin signaling pathway. Consistently, CDK5-SV could also interact with β-catenin as CDK5 does. Taken together, our findings suggest that CDK5-SV might also be a negative regulator of Wnt/β-catenin signaling pathway.

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Abbreviations

CDK:

Cyclin-dependent kinase

CDK5-SV:

Cyclin-dependent kinase 5- splicing variant

β-MG:

β-Macroglobin

Wnt:

Wingless-type MMTV integration site family

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Acknowledgments

This work was supported by the National 973 program of China (2004CB518605), the National 863 project of China (2006AA020501), the National Key Sci-Tech Special Project of China (2008ZX10002-020), the Project of the Shanghai Municipal Science and Technology Commission (03dz14086) and the National Natural Science foundation of China (30024001, 30771188).

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Authors and Affiliations

  1. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Road, 200433, Shanghai, People’s Republic of China

    Qiang Li, Xianghua Liu, Mingjun Zhang, Guangming Ye, Qian Qiao, Yichen Ling, Yanhua Wu, Yuanyuan Zhang & Long Yu

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  1. Qiang Li
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  2. Xianghua Liu
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  3. Mingjun Zhang
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  4. Guangming Ye
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  5. Qian Qiao
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  6. Yichen Ling
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  7. Yanhua Wu
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  8. Yuanyuan Zhang
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  9. Long Yu
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Correspondence to Long Yu.

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Qiang Li and Xianghua Liu contributed equally to this work.

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Li, Q., Liu, X., Zhang, M. et al. Characterization of a novel human CDK5 splicing variant that inhibits Wnt/β-catenin signaling. Mol Biol Rep 37, 2415–2421 (2010). https://doi.org/10.1007/s11033-009-9752-7

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  • DOI: https://doi.org/10.1007/s11033-009-9752-7

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