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E3 ubiquitin ligase Cullin4B mediated polyubiquitination of p53 for its degradation

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Abstract

Controlled protein ubiquitination through E3 ubiquitin ligases and degradation via 26S proteasome machinery is required for orderly progression through cell cycle, chromatin remodeling, DNA repair, and development. Each cullin-dependent ubiquitin ligase (E3) complex can recruit various substrates for their degradation. Cullin 4A (CUL4A) and Cullin 4B (CUL4B) are members of cullin family proteins that mediate ubiquitin dependent proteolysis. Though, these two cul4 genes are functionally redundant, Cullin 4B is not a substitute for all the Cullin 4A functions. Published report has shown that CUL4A interacts with p53 and induces its decay. Although, CUL4A has been known to control several cellular processes, little is known about CUL4B functions. Therefore, in this study, we analyzed the role of CUL4B on p53 polyubiquitination. Our stable cell line and transient transfection studies show that CUL4B indeed interacts with p53 and induces its polyubiquitination. Importantly, both CUL4A and CUL4B overexpressing cells show almost equal levels of p53 polyubiquitination. Moreover, we observed an increased level of polyubiquitination on p53 in CUL4B overexpressing stable cell line upon treatment with siRNA specific for CUL4A indicating that CUL4B plays a vital role in p53 stability. In addition, we have observed the differential expression of CUL4B in various eukaryotic cell lines and mouse tissues suggesting the important role of CUL4B in various tissues. Together, these observations establish an important negative regulatory role of CUL4B on p53 stability.

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Acknowledgments

We are very grateful to Prof. Pradip Raychaudhuri for providing necessary plasmids used in this study. We express sincere thanks to Dr. Srilata Bagchi for technical advice and constant support. I especially thank Dr. Arunkumar Dhayalan for critical reading of the manuscript. This work is supported by Department of Science and Technology-SERB, INDIA grants; SB/EMEQ: 038/2013 and SR/FT/LS 76/2011 to SB.

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Authors and Affiliations

  1. Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India

    Anand Thirunavukarasou, Prachi Singh, Gokulapriya Govindarajalu, Venkateshwarlu Bandi & Sudhakar Baluchamy

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  1. Anand Thirunavukarasou
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  2. Prachi Singh
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Correspondence to Sudhakar Baluchamy.

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Thirunavukarasou, A., Singh, P., Govindarajalu, G. et al. E3 ubiquitin ligase Cullin4B mediated polyubiquitination of p53 for its degradation. Mol Cell Biochem 390, 93–100 (2014). https://doi.org/10.1007/s11010-014-1960-3

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  • DOI: https://doi.org/10.1007/s11010-014-1960-3

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