Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner.
Alternative splicing of cyclin D1 gene mRNA has recently been demonstrated. The novel transcript shows no splicing at the downstream exon 4 boundary and encodes a protein with an altered carboxyl-terminal domain that is a cyclin D1 variant; exon 5 is not included in the coding sequence which terminates downstream of exon 4. We here produced cells that exogenously express each form of cyclin D1 and analysed their cell cycle regulation. We found that (1) alternative splicing forms of cyclin D1 modulated entry into the cell cycle in an inverse manner; (2) both splicing forms suppressed cell growth; and (3) cells overexpressing form [a] were inhibited from entry into and completion of the S phase, although form [b]-expressing cells showed no reduction of G1- to S transition. We also found that overexpression of either cyclin D1 form upregulated Rb gene products, suggesting that this upregulation may be one of the causes of growth suppression in cyclin D1 overexpressing cells.
Sawa
H
H
Department of Neurosurgery, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Ohshima
T A
TA
Ukita
H
H
Murakami
H
H
Chiba
Y
Y
Kamada
H
H
Hara
M
M
Saito
I
I
D017398:Alternative Splicing; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D019938:Cyclin D1 / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D005434:Flow Cytometry; D016193:G1 Phase; D005786:Gene Expression Regulation; D016158:Genes, p53; D005910:Glioma / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008869:Microtubule-Associated Proteins / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011518:Proto-Oncogene Proteins; D016192:Resting Phase, Cell Cycle; D016160:Retinoblastoma Protein / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D001973:Bromodeoxyuridine