A novel candidate oncogene, MCT-1, is involved in cell cycle progression.
Using the arbitrarily primed-PCR (AP-PCR) assay to detect genetic abnormalities that occur in a panel of lymphoid cell lines, we identified an amplified stretch of genomic DNA that contained a putative open reading frame. Northern blot analysis with this genomic clone revealed widespread low level expression in normal human tissue. The full cDNA sequence was obtained with no significant homology to any known genes in the genome database. We termed this novel gene with multiple copies in a T-cell malignancy as MCT-1. MCT-1 was localized to the long arm of chromosome Xq22-24 by flourescence in situ hybridization analysis. Although there was no significant homology at the primary sequence level, there was a limited degree of amino acid homology with a domain of cyclin H that appears to specify protein-protein complexes. This relationship between MCT-1 and cyclin H implied a potential role for MCT-1 in cell cycle regulation. Overexpression of MCT-1 increased the proliferative rate of cells by decreasing the length of the G1 phase without a reciprocal increase in the S and G2-M phases. Recent work has established the role of cell cycle regulatory molecules in the development of certain human malignancies. Therefore, we investigated the transforming ability of MCT-1 overexpression using soft agar growth assays and demonstrated that only MCT-1-overexpressing cells were able to establish colonies. Taken together, MCT-1 is a novel candidate oncogene with homology to a protein-protein binding domain of cyclin H.
Center for NeuroVirology and NeuroOncology, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19102, USA.
M
M
Prosniak
J
J
Dierov
K
K
Okami
B
B
Tilton
B
B
Jameson
B E
BE
Sawaya
R B
RB
Gartenhaus
D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D056748:Cyclin H; D016213:Cyclins / Q000737:chemistry; D018076:DNA, Complementary; D006801:Humans; D007621:Karyotyping; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D009857:Oncogenes; D016133:Polymerase Chain Reaction / Q000379:methods; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D014960:X Chromosome
C534751:CCNH protein, human; D018797:Cell Cycle Proteins; D056748:Cyclin H; D016213:Cyclins; D018076:DNA, Complementary; C115081:MCTS1 protein, human; D015513:Oncogene Proteins