Genomic organization, chromosomal localization, and independent expression of human cyclin D genes.

Murine cDNA clones for three cyclin D genes that are normally expressed during the G1 phase of the cell cycle were used to clone the cognate human genes. Bacteriophage and cosmid clones encompassing five independent genomic loci were partially sequenced and chromosomally assigned by an analysis of somatic cell hybrids containing different human chromosomes and by fluorescence in situ hybridization to metaphase spreads from normal peripheral blood lymphocytes. The human cyclin D1 gene (approved gene symbol, CCND1) was assigned to chromosome band 11q13, cyclin D2 (CCND2) to chromosome band 12p13, and cyclin D3 (CCND3) to chromosome band 6p21. Pseudogenes containing sequences related to cyclin D2 and cyclin D3 mapped to chromosome bands 11q13 and 6p21, respectively. Partial nucleotide sequence analysis of exons within each gene revealed that the authentic human cyclin D genes are more related to their mouse counterparts than to each other. These genes are ubiquitously transcribed in human tumor cell lines derived from different cell lineages, but are independently and, in many cases, redundantly expressed. The complex patterns of expression of individual cyclin D genes and their evolutionary conservation across species suggest that each family member may play a distinct role in cell cycle progression.

[1]  G. Tokiwa,et al.  The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. , 1988, The EMBO journal.

[2]  P. Leder,et al.  Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Reed,et al.  A family of cyclin homologs that control the G1 phase in yeast. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Tony Hunter,et al.  Isolation of a human cyclin cDNA: Evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2 , 1989, Cell.

[5]  Curt Wittenberg,et al.  An essential G1 function for cyclin-like proteins in yeast , 1989, Cell.

[6]  G. Moore,et al.  Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. , 1972, Journal of the National Cancer Institute.

[7]  R. Eddy,et al.  Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma. , 1989, The Journal of clinical investigation.

[8]  S. Reed,et al.  Isolation of three novel human cyclins by rescue of G1 cyclin (cln) function in yeast , 1991, Cell.

[9]  D. Pinkel,et al.  Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[10]  H. Koeffler,et al.  An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1). , 1980, Blood.

[11]  Richard A. Ashmun,et al.  Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle , 1991, Cell.

[12]  C. Alvarado,et al.  Two new acute lymphoblastic leukemia cell lines with early B-cell phenotypes , 1982 .

[13]  E. Harlow,et al.  The retinoblastoma protein is phosphorylated during specific phases of the cell cycle , 1989, Cell.

[14]  B. Horsthemke,et al.  Mechanism of i(6p) formation in retinoblastoma tumor cells. , 1989, Cancer genetics and cytogenetics.

[15]  D. Beach,et al.  The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis , 1988, Cell.

[16]  D. Birnbaum,et al.  Amplification of FGF-related genes in human tumors: possible involvement of HST in breast carcinomas. , 1989, Oncogene.

[17]  O. Melnyk,et al.  Characterization of a candidate bcl-1 gene , 1991, Molecular and cellular biology.

[18]  S. Raimondi,et al.  Nonrandom involvement of the 12p12 breakpoint in chromosome abnormalities of childhood acute lymphoblastic leukemia , 1986 .

[19]  M. Valentine,et al.  t(11;22) and other chromosomal rearrangements in Ewing's sarcoma. , 1986, Journal of the National Cancer Institute.

[20]  P. Houghton,et al.  A specific chromosomal abnormality in rhabdomyosarcoma. , 1987, Cytogenetics and cell genetics.

[21]  J. Labbé,et al.  MPF from starfish oocytes at first meiotic metaphase is a heterodimer containing one molecule of cdc2 and one molecule of cyclin B. , 1989, The EMBO journal.

[22]  S. Collins,et al.  Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[23]  A. Arnold,et al.  A novel cyclin encoded by a bcl1-linked candidate oncogene , 1991, Nature.

[24]  W. Rutter,et al.  Rat insulin genes: construction of plasmids containing the coding sequences. , 1977, Science.

[25]  L. Meijer,et al.  cdc2 is a component of the M phase-specific histone H1 kinase: Evidence for identity with MPF , 1988, Cell.

[26]  D. Beach,et al.  Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: Evidence for multiple roles of mitotic cyclins , 1991, Cell.

[27]  D. Birnbaum,et al.  Chromosomal localization of the hst oncogene and its co-amplification with the int.2 oncogene in a human melanoma. , 1988, Oncogene.

[28]  J. Ruderman,et al.  The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes , 1986, Cell.

[29]  K. Offit,et al.  Molecular analysis of breaks in BCL-1 proto-oncogene in B-cell lymphomas with abnormalities of 11q13. , 1989, Oncogene.

[30]  Tony Hunter,et al.  Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B , 1990, Nature.

[31]  T. Hunt,et al.  Cyclin synthesis, modification and destruction during meiotic maturation of the starfish oocyte. , 1987, Developmental biology.

[32]  J. Yokota,et al.  Human HST1 (HSTF1) gene maps to chromosome band 11q13 and coamplifies with the INT2 gene in human cancer. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[33]  T. Hunter,et al.  Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport , 1991, The Journal of cell biology.

[34]  David Beach,et al.  cdc2 protein kinase is complexed with both cyclin A and B: Evidence for proteolytic inactivation of MPF , 1989, Cell.

[35]  Jean Gautier,et al.  Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2 + , 1988, Cell.

[36]  David M. Livingston,et al.  The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element , 1989, Cell.

[37]  E. Schuuring,et al.  D11S287, a putative oncogene on chromosome 11q13, is amplified and expressed in squamous cell and mammary carcinomas and linked to BCL-1. , 1991, Oncogene.

[38]  F. Cross,et al.  DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae , 1988, Molecular and cellular biology.

[39]  J. Maller,et al.  Role for cyclin A in the dependence of mitosis on completion of DMA replication , 1991, Nature.

[40]  T. Shows,et al.  Rearrangement and overexpression of D11S287E, a candidate oncogene on chromosome 11q13 in benign parathyroid tumors. , 1991, Oncogene.

[41]  G. Peters,et al.  Gene amplification on chromosome band 11q13 and oestrogen receptor status in breast cancer. , 1990, European journal of cancer.

[42]  L. Deaven,et al.  Reassignment of the human CSF1 gene to chromosome 1p13-p21. , 1991, Blood.

[43]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[44]  E. Rosenthal,et al.  Selective translation of mRNA controls the pattern of protein synthesis during early development of the surf clam, Spisula solidissima , 1980, Cell.

[45]  P. Thomas,et al.  Hybridization of denatured RNA transferred or dotted nitrocellulose paper. , 1983, Methods in enzymology.

[46]  M. Meyerson,et al.  Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase , 1991, Nature.

[47]  G. Merlo,et al.  Expression of int-2 mRNA in human tumors amplified at the int-2 locus. , 1989, Oncogene.

[48]  W. Lee,et al.  Retinoblastoma cancer suppressor gene product is a substrate of the cell cycle regulator cdc2 kinase. , 1991, The EMBO journal.

[49]  P. Nowell,et al.  Clustering of breakpoints on chromosome 11 in human B-cell neoplasms with the t(11 ; 14) chromosome translocation , 1985, Nature.

[50]  A. V. D. van den Ouweland,et al.  Human c-fms proto-oncogene: comparative analysis with an abnormal allele , 1985, Molecular and cellular biology.

[51]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[52]  James M. Roberts,et al.  Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family , 1991, Cell.

[53]  B. Franza,et al.  A 60 kd cdc2-associated polypeptide complexes with the E1A proteins in adenovirus-infected cells , 1989, Cell.

[54]  Jeremy Minshull,et al.  Cyclin is a component of maturation-promoting factor from Xenopus , 1990, Cell.

[55]  Anne Fernandez,et al.  Cyclin a is required for the onset of DNA replication in mammalian fibroblasts , 1991, Cell.

[56]  S. Colowick,et al.  Methods in Enzymology , Vol , 1966 .

[57]  J. Labbé,et al.  Purification of MPF from starfish: Identification as the H1 histone kinase p34cdc2 and a possible mechanism for its periodic activation , 1989, Cell.

[58]  M. Kirschner,et al.  Cyclin in fission yeast , 1988, Cell.

[59]  P. Nowell,et al.  The chromosome 14 breakpoint in neoplastic B cells with the t(11;14) translocation involves the immunoglobulin heavy chain locus. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Eric T. Rosenthal,et al.  Cyclin: A protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division , 1983, Cell.

[61]  L. Meijer,et al.  Cyclin is a component of the sea urchin egg M‐phase specific histone H1 kinase. , 1989, The EMBO journal.

[62]  T. Papayannopoulou,et al.  HEL cells: a new human erythroleukemia cell line with spontaneous and induced globin expression. , 1982, Science.

[63]  Phang-lang Chen,et al.  Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation , 1989, Cell.

[64]  B. Futcher,et al.  Human D-type cyclin , 1991, Cell.