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The helix–loop–helix protein ID1 localizes to centrosomes and rapidly induces abnormal centrosome numbers

Oncogene volume 23, pages 1930–1938 (2004)Cite this article

Abstract

ID1 is a member of the inhibitor of DNA binding/differentiation (ID) family of dominant negative helix–loop–helix transcription factors. ID-proteins have been implicated in the control of differentiation and transcriptional modulation of various cell cycle regulators and high levels of ID1 expression are frequently detected in various cancer types. However, it is unclear whether ID1 is a marker of highly proliferative cancer cells or whether it directly contributes to the tumor phenotype. A detailed analysis of ID1-expressing human cells revealed that a fraction of ID1 localizes to centrosomes. Ectopic expression of ID1 in primary cells and tumor cell lines resulted in accumulation of cells with abnormal centrosome numbers. There was no evidence for centrosomal localization or induction of centrosome abnormalities by the other ID family members. Hence, ID1 may contribute to oncogenesis not only by inhibiting transcriptional activity of basic helix–loop–helix transcription factors and abrogate differentiation but also by subverting centrosome duplication.

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Acknowledgements

We thank M Bornens for the centrin-GFP construct, S Piboonniyom for normal oral keratinocytes, R Benezra for ID1−/− MEFs, and E B Affar for wild-type MEFs. JH is especially grateful for the extraordinary support of Katja Hasskarl. This work was supported by Public Health Service Grant R01 CA66980 (KM), and by postdoctoral fellowships HA3185/1-1 and DU343/1-1 from the Deutsche Forschungsgemeinschaft to JH and SD, respectively.

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Author notes

  1. Jens Hasskarl

    Present address: Hematology/Oncology Division, University of Freiburg Medical Center, 79106, Freiburg, Germany

  2. Stefan Duensing

    Present address: Molecular Virology Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA, 15213, USA

  3. Jens Hasskarl and Stefan Duensing: These authors contributed equally

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  1. Department of Pathology, Harvard Medical School, Boston, 02115, MA, USA

    Jens Hasskarl, Stefan Duensing, Edwin Manuel & Karl Münger

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  1. Jens Hasskarl
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Correspondence to Karl Münger.

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Hasskarl, J., Duensing, S., Manuel, E. et al. The helix–loop–helix protein ID1 localizes to centrosomes and rapidly induces abnormal centrosome numbers. Oncogene 23, 1930–1938 (2004). https://doi.org/10.1038/sj.onc.1207310

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