Abstract
G1 cyclin E controls the initiation of DNA synthesis by activating CDK2, and abnormally high levels of cyclin E expression have frequently been observed in human cancers. We have isolated a novel human cyclin, cyclin E2, that contains significant homology to cyclin E. Cyclin E2 specifically interacts with CDK inhibitors of the CIP/KIP family and activates both CDK2 and CDK3. The expression of cyclin E2 mRNA oscillates periodically throughout the cell cycle, peaking at the G1/S transition, and exhibits a pattern of tissue specificity distinct from that of cyclin E1. Cyclin E2 encodes a short lived protein whose turnover is most likely governed by the proteasome pathway and is regulated by phosphorylation on a conserved Thr-392 residue. Expression of the viral E6 oncoprotein in normal human fibroblasts increases the steady state level of cyclin E2, but not cyclin E1, while expression of the E7 oncoprotein upregulates both. These data suggest that the expression of these two G1 E-type cyclins may be similarly regulated by the pRb function, but distinctly by the p53 activity.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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CDC2-CDC28 Kinases*
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Cell Transformation, Viral / genetics*
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Cloning, Molecular
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 3
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Cyclin-Dependent Kinases / metabolism*
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Cyclins / biosynthesis
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Cyclins / genetics
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Cyclins / physiology*
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Cysteine Endopeptidases / metabolism
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DNA, Complementary / genetics
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Enzyme Activation
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Fibroblasts / cytology
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Fibroblasts / metabolism
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G1 Phase / genetics*
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Gene Expression Regulation
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Gene Expression Regulation, Viral*
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Genes
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Half-Life
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Humans
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Molecular Sequence Data
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Multienzyme Complexes / metabolism
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Oncogene Proteins, Viral / physiology*
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Organ Specificity
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Phosphorylation
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Phosphothreonine / metabolism
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Proteasome Endopeptidase Complex
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Protein Processing, Post-Translational
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Protein Serine-Threonine Kinases / metabolism*
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Retinoblastoma Protein / physiology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Tumor Suppressor Protein p53 / physiology
Substances
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CCNE2 protein, human
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Cyclins
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DNA, Complementary
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Multienzyme Complexes
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Oncogene Proteins, Viral
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RNA, Messenger
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Retinoblastoma Protein
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Tumor Suppressor Protein p53
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Phosphothreonine
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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CDK2 protein, human
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CDK3 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 3
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Cyclin-Dependent Kinases
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex