title: RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignancies.
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 II 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 immunodeficient mice, and dephosphorylation of ppRB by RBSP3/HYA22, presumably leading to a block of the cell cycle at the G1/S boundary.
authors.affiliation: Microbiology and Tumor Biology Center and Center for Genomics and Bioinformatics, Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Kashuba
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Li
authors.forename: Fuli
authors.initials: F
authors.lastname: Wang
authors.forename: Vera N
authors.initials: VN
authors.lastname: Senchenko
authors.forename: Alexey
authors.initials: A
authors.lastname: Protopopov
authors.forename: Alena
authors.initials: A
authors.lastname: Malyukova
authors.forename: Alexey S
authors.initials: AS
authors.lastname: Kutsenko
authors.forename: Elena
authors.initials: E
authors.lastname: Kadyrova
authors.forename: Veronika I
authors.initials: VI
authors.lastname: Zabarovska
authors.forename: Olga V
authors.initials: OV
authors.lastname: Muravenko
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Zelenin
authors.forename: Lev L
authors.initials: LL
authors.lastname: Kisselev
authors.forename: Igor
authors.initials: I
authors.lastname: Kuzmin
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Gösta
authors.initials: G
authors.lastname: Winberg
authors.forename: Ingemar
authors.initials: I
authors.lastname: Ernberg
authors.forename: Eleonora
authors.initials: E
authors.lastname: Braga
authors.forename: Michael I
authors.initials: MI
authors.lastname: Lerman
authors.forename: George
authors.initials: G
authors.lastname: Klein
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Zabarovsky
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D017931:DNA Primers; D015342:DNA Probes; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D017386:Sequence Homology, Amino Acid; D016324:Sequence Tagged Sites; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: C486483:CTDSPL protein, human; D017931:DNA Primers; D015342:DNA Probes; D025521:Tumor Suppressor Proteins