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Interference of the dominant negative helix–loop–helix protein ID1 with the proteasomal subunit S5A causes centrosomal abnormalities

Oncogene volume 27, pages 1657–1664 (2008)Cite this article

Abstract

The inhibitor of DNA-binding (ID) proteins are dominant-negative inhibitors of basic helix–loop–helix transcription factors that have multiple functions during development and cellular differentiation. High-level expression of some ID family members has been observed in human malignancies, and in some cases was correlated with poor clinical prognosis. Ectopic ID1 expression extends the life span of primary human epithelial cells, inhibits cellular differentiation and induces centrosome duplication errors, thus suggesting that ID1 may have oncogenic activities. ID1 can bind to the proteasomal subunit S5A/Rpn10, but the biological consequences of the interaction have not been studied in detail. Here, we show that ID1's ability to induce supernumerary centrosomes correlates with S5A binding. Similar to ID1, a fraction of the S5A protein localizes to centrosomal structures. Furthermore, partial depletion of S5A by RNA interference causes accumulation of cells with supernumerary centrosomes. These results are consistent with the model that ID1 dysregulates centrosome homeostasis at least in part by interfering with S5A activities at the centrosome.

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Acknowledgements

We thank M Bornens for the centrin-GFP construct, R Agami for pSUPER.retro, PM Howley for S5A cDNA, and S Duensing for helpful discussion. We thank N Bourgeois for technical assistance. JH is especially grateful for the extraordinary support of K Hasskarl. This work was supported by Public Health Service Grant R01 CA066980 (KM), by postdoctoral fellowship HA3185/1-1 and research Grant HA3185/2-1 and 2-3 from the Deutsche Forschungsgemeinschaft (JH).

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Authors and Affiliations

  1. Division of Hematology and Oncology, University of Freiburg Medical Center, Freiburg im Breisgau, Germany

    J Hasskarl & D S Mern

  2. The Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA

    K Münger

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  1. J Hasskarl
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Correspondence to J Hasskarl.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Hasskarl, J., Mern, D. & Münger, K. Interference of the dominant negative helix–loop–helix protein ID1 with the proteasomal subunit S5A causes centrosomal abnormalities. Oncogene 27, 1657–1664 (2008). https://doi.org/10.1038/sj.onc.1210808

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