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RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignancies

  1. Author:
    Kashuba, V. I.
    Li, J. F.
    Wang, F. L.
    Senchenko, V. N.
    Protopopov, A.
    Malyukova, A.
    Kutsenko, A. S.
    Kadyrova, E.
    Zabarovska, V. I.
    Muravenko, O. V.
    Zelenin, A. V.
    Kisselev, L. L.
    Kuzmin, I.
    Minna, J. D.
    Winberg, G.
    Ernberg, I.
    Braga, E.
    Lerman, M. I.
    Klein, G.
    Zabarovsky, E. R.

  2. Author Address

    Zabarovsky, ER, Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden. Karolinska Inst, Ctr Genom & Bioinformat, S-17177 Stockholm, Sweden. Ukrainian Acad Sci, Inst Mol Biol & Genet, UA-252627 Kiev, Ukraine. Russian Acad Sci, Ctr Bioengn, Moscow 117312, Russia. Russian State Genet Ctr, Moscow 117545, Russia. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia. NCI, Canc Causing Genes Sect, Immunobiol Lab, Canc Res Ctr, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA.
    1. Year: 2004
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 101
    2. 14
    3. Pages: 4906-4911
  4. Type of Article: Article
  1. Abstract:

    Chromosome 3p21.3 region is frequently (>90%) deleted in lung and other major human carcinomas. We subdivided 3p21.3 into LUCA and AP20 subregions and discovered frequent homozygous deletions (10-18%) in both subregions. This finding strongly implies that they harbor multiple tumor suppressor genes involved in the origin and/or development of major epithelial cancers. In this study, we performed an initial analysis of RBSP3/HYA22, a candidate tumor suppressor genes located in the AP20 region. Two sequence splice variants of RBSP3/HYA22 (A and B) were identified, and we provide evidence for their tumor suppressor function. By sequence analysis RBSP3/HYA22 belongs to a gene family of small C-terminal domain phosphatases that may control the RNA polymerase 11 transcription machinery. Expression of the gene was drastically (>20-fold) decreased in 11 of 12 analyzed carcinoma cell lines and in three of eight tumor biopsies. We report missense and nonsense mutations in tumors where RBSP3/HYA22 was expressed, growth suppression with regulated transgenes in culture, suppression of tumor formation in severe combined immundeficient mice, and dephosphorylation of ppRB by RBSP3/HYA22, presumably leading to a block of the cell cycle at the G(1)/S boundary

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