RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignancies.
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.
Kashuba
Vladimir I
VI
Microbiology and Tumor Biology Center and Center for Genomics and Bioinformatics, Karolinska Institute, 17177 Stockholm, Sweden.
Li
Jingfeng
J
Wang
Fuli
F
Senchenko
Vera N
VN
Protopopov
Alexey
A
Malyukova
Alena
A
Kutsenko
Alexey S
AS
Kadyrova
Elena
E
Zabarovska
Veronika I
VI
Muravenko
Olga V
OV
Zelenin
Alexander V
AV
Kisselev
Lev L
LL
Kuzmin
Igor
I
Minna
John D
JD
Winberg
Gösta
G
Ernberg
Ingemar
I
Braga
Eleonora
E
Lerman
Michael I
MI
Klein
George
G
Zabarovsky
Eugene R
ER
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
C486483:CTDSPL protein, human; D017931:DNA Primers; D015342:DNA Probes; D025521:Tumor Suppressor Proteins