Characterization of a second human cyclin A that is highly expressed in testis and in several leukemic cell lines.
In this study, we isolated and characterized a human cyclin A-like gene that we named cyclin A1. Cyclin A1 has 48% identity with human cyclin A and is more related to the recently cloned murine cyclin A1 (84% identity). The human cyclin A1 is specifically expressed in testis and brain among all of the normal tissues that we studied by Northern blot analysis; in addition, it is expressed in several myeloid leukemia cell lines, including ML-1, U937, NB4, KG-1, and THP1. A sensitive reverse transcription-PCR-Southern blot method also detected low-level expression of this gene in many other hematopoietic and nonhematopoietic cell lines. The expression of cyclin A1 mRNA is differentiation- and cell cycle-regulated in the ML-1 cells. We raised polyclonal antibodies against a glutathione S-transferase-cyclin A1 fusion protein produced in Escherichia coli. In immunoblot analyses, the antibodies recognized the Mr 65,000 cyclin A1 protein in ML-1 cells. The anti-cyclin A1 also immunoprecipitated the Mr 65,000 cyclin A1, along with the Mr 33,000 cyclin-dependent kinase (CDK) 2 and other proteins at Mr 39,000, 42,000, 45,000, 95,000, and 110,000. In an in vitro kinase assay, the CDK2-cyclin A1 complex precipitated by anti-cyclin A1 showed kinase activities against histone H1. In a yeast two-hybrid assay, cyclin A1 can bind to CDK2 but not to CDC2, CDK4, and CDK5. We mapped the human cyclin A1 gene to chromosome 13q12.3-q13, approximately 1000 kb from the sequence-tagged site marker WI-3374.
Yang
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Division of Hematology/Oncology, Cedars-Sinai Research Institute, University of California at Los Angeles School of Medicine, 90048, USA.
Morosetti
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Koeffler
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HP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D002454:Cell Differentiation; D002882:Chromosomes, Human, Pair 13; D003001:Cloning, Molecular; D019925:Cyclin A; D056750:Cyclin A1; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D006410:Hematopoiesis; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000502:physiology*; D029867:Xenopus Proteins; D014982:Xenopus laevis
C503745:CCNA1 protein, human; C503747:Ccna1 protein, mouse; D019925:Cyclin A; D056750:Cyclin A1; D016213:Cyclins; D012333:RNA, Messenger; D029867:Xenopus Proteins; D011494:Protein Kinases; C102333:histone H1 kinase; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495891:Cdk2 protein, Xenopus; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases