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Tob2, a novel anti-proliferative Tob/BTG1 family member, associates with a component of the CCR4 transcriptional regulatory complex capable of binding cyclin-dependent kinases

Oncogene volume 18, pages 7432–7441 (1999)Cite this article

Abstract

Human cDNAs encoding a novel member of Tob/BTG1 anti-proliferative family proteins were cloned. The putative protein product termed Tob2 consisted of 344 amino acids with high similarity to the Tob protein. The tob2 mRNA was 4.1 kb long and was ubiquitously expressed in human adult tissues, as was revealed by Northern blot hybridization. However, further in situ hybridization analysis showed a characteristic expression of the tob2 mRNA in oocytes, suggesting a unique role of Tob2 in oogenesis. Like the Tob protein, Tob2 inhibited cell cycle progression from the G0/G1 to S phases. Intriguingly, the amino-terminal half of Tob2 as well as that of Tob was associated with a human homologue of yeast Caf1, a component of the CCR4 transcription factor complex. Moreover, Caf1 was associated with cyclin dependent kinases. These data suggested that both Tob and Tob2 were involved in cell cycle regulation through their interaction with Caf1. Finally, the tob2 gene was mapped to human chromosome 22q13.1-q13.31.

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Acknowledgements

This work was initiated by S Matsuda. We thank S Matsuda, J Inoue, H Umemori, S Kuramochi, T Ishida, T Tezuka and M Kim for technical support and valuable discussions. We also thank S Mori and Y Morishita for technical advice and helpful discussions. We appreciate A Tanaka for critical reading of the manuscript. This work was supported in part by a grant for Advanced Cancer Research from the Ministry of Education, Science, Sports and Culture of Japan and the Program for the Promotion of Fundamental Studies in Health Science of Organization for Drug ADR Relief, R&D Promotion and Product Review of Japan.

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Authors and Affiliations

  1. Department of Oncology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan

    Naoko Ikematsu, Yutaka Yoshida, Junko Kawamura-Tsuzuku, Miho Ohsugi, Masanori Onda, Jiro Fujimoto & Tadashi Yamamoto

  2. Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Momoki Hirai

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  1. Naoko Ikematsu
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Ikematsu, N., Yoshida, Y., Kawamura-Tsuzuku, J. et al. Tob2, a novel anti-proliferative Tob/BTG1 family member, associates with a component of the CCR4 transcriptional regulatory complex capable of binding cyclin-dependent kinases. Oncogene 18, 7432–7441 (1999). https://doi.org/10.1038/sj.onc.1203193

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