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

被引:74
作者
Kashuba, VI
Li, JF
Wang, FL
Senchenko, VN
Protopopov, A
Malyukova, A
Kutsenko, AS
Kadyrova, E
Zabarovska, VI
Muravenko, OV
Zelenin, AV
Kisselev, LL
Kuzmin, I
Minna, JD
Winberg, G
Ernberg, I
Braga, E
Lerman, MI
Klein, G
Zabarovsky, ER [1 ]
机构
[1] Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Ctr Genom & Bioinformat, S-17177 Stockholm, Sweden
[3] Ukrainian Acad Sci, Inst Mol Biol & Genet, UA-252627 Kiev, Ukraine
[4] Russian Acad Sci, Ctr Bioengn, Moscow 117312, Russia
[5] Russian State Genet Ctr, Moscow 117545, Russia
[6] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia
[7] NCI, Canc Causing Genes Sect, Immunobiol Lab, Canc Res Ctr, Frederick, MD 21702 USA
[8] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA
[9] Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA
关键词
D O I
10.1073/pnas.0401238101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4906 / 4911
页数:6
相关论文
共 23 条
  • [1] Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3
    Dammann, R
    Li, C
    Yoon, JH
    Chin, PL
    Bates, S
    Pfeifer, GP
    [J]. NATURE GENETICS, 2000, 25 (03) : 315 - 319
  • [2] The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis
    Dreijerink, K
    Braga, E
    Kuzmin, I
    Geil, L
    Duh, FM
    Angeloni, D
    Zbar, B
    Lerman, MI
    Stanbridge, EJ
    Minna, JD
    Protopopov, A
    Li, JF
    Kashuba, V
    Klein, G
    Zabarovsky, ER
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (13) : 7504 - 7509
  • [3] IDENTIFICATION OF PROTEIN CODING REGIONS BY DATABASE SIMILARITY SEARCH
    GISH, W
    STATES, DJ
    [J]. NATURE GENETICS, 1993, 3 (03) : 266 - 272
  • [4] Search for unknown tumor-antagonizing genes
    Imreh, S
    Klein, G
    Zabarovsky, ER
    [J]. GENES CHROMOSOMES & CANCER, 2003, 38 (04) : 307 - 321
  • [5] Ishikawa S, 1997, DNA Res, V4, P35, DOI 10.1093/dnares/4.1.35
  • [6] Kok K, 1997, ADV CANCER RES, V71, P27, DOI 10.1016/S0065-230X(08)60096-2
  • [7] Lerman MI, 2000, CANCER RES, V60, P6116
  • [8] Notl subtraction and Notl-specific microarrays to detect copy number and methylation changes in whole genomes
    Li, JF
    Protopopov, A
    Wang, FL
    Senchenko, V
    Petushkov, V
    Vorontsova, O
    Petrenko, L
    Zabarovska, V
    Muravenko, O
    Braga, E
    Kisselev, L
    Lerman, MI
    Kashuba, V
    Klein, G
    Ernberg, I
    Wahlestedt, C
    Zabarovsky, ER
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (16) : 10724 - 10729
  • [9] Identification of new tumor suppressor genes based on in vivo functional inactivation of a candidate gene
    Li, JF
    Protopopov, AI
    Gizatullin, RZ
    Kiss, C
    Kashuba, VI
    Winberg, G
    Klein, G
    Zabarovsky, ER
    [J]. FEBS LETTERS, 1999, 451 (03) : 289 - 294
  • [10] Proteasome inhibitor induces nucleolar translocation of Epstein-Barr virus-encoded EBNA-5
    Pokrovskaja, K
    Mattsson, K
    Kashuba, E
    Klein, G
    Szekely, L
    [J]. JOURNAL OF GENERAL VIROLOGY, 2001, 82 : 345 - 358