Human papillomavirus type 16 (HPV16) can cause cervical cancer. Expression of the viral E1(boolean AND)E4 protein is lost during malignant progression, but in premalignant lesions, E1(boolean AND)E4 is abundant in cells supporting viral DNA amplification. Expression of 16E1(boolean AND)E4 in cell culture causes G(2) cell cycle arrest. Here we show that unlike many other G(2) arrest mechanisms, 16E1(boolean AND)E4 does not inhibit the kinase activity of the Cdk1/cyclin B1 complex. Instead, 16E1(boolean AND)E4 uses a novel mechanism in which it sequesters Cdk1/cyclin B1 onto the cytokeratin network. This prevents the accumulation of active Cdk1/cyclin B1 complexes in the nucleus and hence prevents mitosis. A mutant 16E1(boolean AND)E4 (T22A, T23A) which does not bind cyclin B1 or alter its intracellular location fails to induce G(2) arrest. The significance of these results is highlighted by the observation that in lesions induced by HPV16, there is evidence for Cdk1/cyclin B1 activity on the keratins of 16E1(boolean AND)E4-expressing cells. We hypothesize that E1(boolean AND)E4-induced G(2) arrest may play a role in creating an environment optimal for viral DNA replication and that loss of E1(boolean AND)E4 expression may contribute to malignant progression.
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
BAKER, CC
PHELPS, WC
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
PHELPS, WC
LINDGREN, V
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
LINDGREN, V
BRAUN, MJ
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
BRAUN, MJ
GONDA, MA
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
GONDA, MA
HOWLEY, PM
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
机构:
Univ Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USAUniv Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USA
Barnes, EA
Kong, M
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Univ Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USAUniv Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USA
Kong, M
Ollendorff, V
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Univ Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USAUniv Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USA
Ollendorff, V
Donoghue, DJ
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Univ Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USAUniv Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USA
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
BAKER, CC
PHELPS, WC
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
PHELPS, WC
LINDGREN, V
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
LINDGREN, V
BRAUN, MJ
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
BRAUN, MJ
GONDA, MA
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
GONDA, MA
HOWLEY, PM
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NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USANCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, CELL & MOLEC STRUCT LAB, FREDERICK, MD 21701 USA
机构:
Univ Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USAUniv Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USA
Barnes, EA
Kong, M
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机构:
Univ Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USAUniv Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USA
Kong, M
Ollendorff, V
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h-index: 0
机构:
Univ Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USAUniv Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USA
Ollendorff, V
Donoghue, DJ
论文数: 0引用数: 0
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机构:
Univ Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USAUniv Calif San Diego, Ctr Mol Genet, Dept Biochem & Chem, La Jolla, CA 92093 USA