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hSSB1 binds and protects p21 from ubiquitin-mediated degradation and positively correlates with p21 in human hepatocellular carcinomas

Oncogene volume 30, pages 2219–2229 (2011)Cite this article

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Abstract

Downregulation of hSSB1, a single-stranded DNA-binding protein, causes increased radiosensitivity, defective checkpoint activation and genomic instability. However, the mechanisms of hSSB1 function in these responses remain to be uncovered. Here, we present evidence that hSSB1 directly binds p21 and this interaction may prevent p21 from ubiquitin-mediated degradation. Furthermore, both promotion of the G1/S transition and abrogation of the G2/M checkpoints induced by hSSB1 knockdown are partially dependent on p21. Most importantly, hSSB1 and p21 levels are positively correlated in human hepatocellular carcinomas (HCC), as determined by immunostaining. Therefore, hSSB1 may positively modulate p21 to regulate cell cycle progression and DNA damage response, implicating hSSB1 as a novel, promising therapeutic target for cancers such as HCC.

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Acknowledgements

We thank the members of the laboratory for their helpful comments on the manuscript. This work was supported by grants from NSFC (30772492 and 30973506 to J-PY, U0732005 to Y-XZ, and 30930045 to TK), from the 863 project (2006AA02A404 to Y-XZ), and from the 973 project (2010CB912201 to TK).

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  1. S Xu, Z Feng and M Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China

    S Xu, Z Feng, M Zhang, Y Wu, Y Sang, H Xu, X Lv, K Hu, J Cao, R Zhang, L Chen, M Liu, J-P Yun, Y-X Zeng & T Kang

  2. Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, China

    S Xu, Y Wu, Y Sang, X Lv, K Hu, J Cao, R Zhang, L Chen, Y-X Zeng & T Kang

  3. Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Z Feng, H Xu & M Liu

  4. Department of pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China

    M Zhang & J-P Yun

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Correspondence to T Kang.

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Xu, S., Feng, Z., Zhang, M. et al. hSSB1 binds and protects p21 from ubiquitin-mediated degradation and positively correlates with p21 in human hepatocellular carcinomas. Oncogene 30, 2219–2229 (2011). https://doi.org/10.1038/onc.2010.596

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