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Identification of Siah-interacting protein as a potential regulator of apoptosis and curcumin resistance

Oncogene volume 29, pages 6357–6366 (2010)Cite this article

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Abstract

The mechanism underlying curcumin (diferuloylmethane) resistance is still largely unknown. Here we employed proteomic approach to identify the Siah-interacting protein (SIP) as a candidate for detailed study, because the spot intensity of SIP on a two-dimensional gel displayed 70–90% reduction in curcumin-sensitive cells, but remained unchanged in curcumin-resistant sublines, after curcumin treatment. Both gain- and loss-of-function studies revealed that SIP promoted curcumin-induced apoptosis. Moreover, SIP underwent phosphorylation and nuclear translocation in curcumin-sensitive but not resistant cells, upon curcumin exposure. The nuclear translocation of SIP was remarkably impaired when a putative nuclear localization sequence (NLS, amino acid (aa) 143–159) was deleted or the serine 141 was mutated into alanine, whereas truncation of the N-terminal region (aa 1–43) obviously increased the nuclear import of SIP. In accordance with their nuclear localization, N-terminal truncation significantly enhanced the proapoptotic effect of SIP, whereas NLS deletion or Ser141Ala mutation attenuated the apoptosis-promoting activity of both wild-type- and N-terminal truncated-SIP. These data suggest that SIP plays a role in apoptosis and curcumin resistance, and the function of SIP may be regulated by different motifs, such as the NLS, N-terminal region and serine 141. Our findings provide new insights into the biological significance of SIP and the mechanisms of drug resistance.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (30470664), Ministry of Science and Technology of China (2010CB912803, 2005CB724600) and Ministry of Education of China (105136).

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Authors and Affiliations

  1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China

    J Luo, J Yang, B-Y Yu & S-M Zhuang

  2. Proteomics Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China

    W Liu & M Li

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  1. J Luo
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Correspondence to S-M Zhuang.

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Luo, J., Yang, J., Yu, BY. et al. Identification of Siah-interacting protein as a potential regulator of apoptosis and curcumin resistance. Oncogene 29, 6357–6366 (2010). https://doi.org/10.1038/onc.2010.358

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