Abstract
Transforming growth factor-β (TGF-β) is a naturally occurring growth inhibitory polypeptide that arrests the cell cycle in middle to late G1 phase. Cells treated with TGF-β contained normal amounts of cyclin E and cyclin-dependent protein kinase 2 (Cdk2) but failed to stably assemble cyclin E-Cdk2 complexes or accumulate cyclin E-associated kinase activity. Moreover, G1 phase extracts from TGF-β-treated cells did not support activation of endogenous cyclin-dependent protein kinases by exogenous cyclins. These effects of TGF-β, which correlated with the inhibition of retinoblastoma protein phosphorylation, suggest that mammalian G1 cyclin-dependent kinases, like their counterparts in yeast, are targets for negative regulators of the cell cycle.
References
71
Referenced
428
- AKIYAMA, T, PHOSPHORYLATION OF THE RETINOBLASTOMA PROTEIN BY CDK2, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 7900 (1992). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1992)
-
ARION, D, CDC2 IS A COMPONENT OF THE M-PHASE SPECIFIC HISTONE-H1 KINASE - EVIDENCE FOR IDENTITY WITH MPF, CELL 55: 371 (1988).
(
10.1016/0092-8674(88)90060-8
) / CELL (1988) -
BLOW, J.J., A CDC2-LIKE PROTEIN IS INVOLVED IN THE INITIATION OF DNA-REPLICATION IN XENOPUS EGG EXTRACTS, CELL 62: 855 (1990).
(
10.1016/0092-8674(90)90261-C
) / CELL (1990) 10.1016/0092-8674(89)90508-4
-
CHANG, F, IDENTIFICATION OF A GENE NECESSARY FOR CELL-CYCLE ARREST BY A NEGATIVE GROWTH-FACTOR OF YEAST - FAR1 IS AN INHIBITOR OF A G1 CYCLIN, CLN2, CELL 63: 999 (1990).
(
10.1016/0092-8674(90)90503-7
) / CELL (1990) 10.1016/0092-8674(89)90517-5
-
CROSS, F, SIMPLE AND COMPLEX CELL-CYCLES, ANNUAL REVIEW OF CELL BIOLOGY 5: 341 (1989).
(
10.1146/annurev.cb.05.110189.002013
) / ANNUAL REVIEW OF CELL BIOLOGY (1989) 10.1016/0092-8674(89)90507-2
-
DESAI, D, ACTIVATION OF HUMAN CYCLIN-DEPENDENT KINASES INVITRO, MOLECULAR BIOLOGY OF THE CELL 3: 571 (1992).
(
10.1091/mbc.3.5.571
) / MOLECULAR BIOLOGY OF THE CELL (1992) 10.1016/0092-8674(88)90175-4
-
DUCOMMUN, B, CDC2 PHOSPHORYLATION IS REQUIRED FOR ITS INTERACTION WITH CYCLIN, EMBO JOURNAL 10: 3311 (1991).
(
10.1002/j.1460-2075.1991.tb04895.x
) / EMBO JOURNAL (1991) 10.1126/science.1329201
-
DUNPHY, W.G., THE XENOPUS CDC2 PROTEIN IS A COMPONENT OF MPF, A CYTOPLASMIC REGULATOR OF MITOSIS, CELL 54: 423 (1988).
(
10.1016/0092-8674(88)90205-X
) / CELL (1988) 10.1126/science.2173140
- ELLEDGE, S.J., CDK2 ENCODES A 33-KDA CYCLIN-A-ASSOCIATED PROTEIN-KINASE AND IS EXPRESSED BEFORE CDC2 IN THE CELL-CYCLE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 2907 (1992). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1992)
-
ENOCH, T, MUTATION OF FISSION YEAST-CELL CYCLE CONTROL GENES ABOLISHES DEPENDENCE OF MITOSIS ON DNA-REPLICATION, CELL 60: 665 (1990).
(
10.1016/0092-8674(90)90669-6
) / CELL (1990) 10.1016/0092-8674(83)90420-8
10.1126/science.1532458
-
FANG, F, EVIDENCE THAT THE G1-S AND G2-M TRANSITIONS ARE CONTROLLED BY DIFFERENT CDC2 PROTEINS IN HIGHER EUKARYOTES, CELL 66: 731 (1991).
(
10.1016/0092-8674(91)90117-H
) / CELL (1991) 10.1073/pnas.87.7.2770
10.1126/science.2237430
-
GAUTIER, J, PURIFIED MATURATION-PROMOTING FACTOR CONTAINS THE PRODUCT OF A XENOPUS HOMOLOG OF THE FISSION YEAST-CELL CYCLE CONTROL GENE CDC2+, CELL 54: 433 (1988).
(
10.1016/0092-8674(88)90206-1
) / CELL (1988) -
GHIARA, J.B., A CYCLIN-B HOMOLOG IN SACCHAROMYCES-CEREVISIAE - CHRONIC ACTIVATION OF THE CDC28 PROTEIN-KINASE BY CYCLIN PREVENTS EXIT FROM MITOSIS, CELL 65: 163 (1991).
(
10.1016/0092-8674(91)90417-W
) / CELL (1991) 10.1016/0092-8674(91)90293-8
-
GOODRICH, D.W., THE RETINOBLASTOMA GENE-PRODUCT REGULATES PROGRESSION THROUGH THE G1 PHASE OF THE CELL-CYCLE, CELL 67: 293 (1991).
(
10.1016/0092-8674(91)90181-W
) / CELL (1991) -
GOULD, K.L., PHOSPHORYLATION AT THR167 IS REQUIRED FOR SCHIZOSACCHAROMYCES-POMBE P34CDC2 FUNCTION, EMBO JOURNAL 10: 3297 (1991).
(
10.1002/j.1460-2075.1991.tb04894.x
) / EMBO JOURNAL (1991) -
GU, Y, CELL-CYCLE REGULATION OF CDK2 ACTIVITY BY PHOSPHORYLATION OF THR160 AND TYR15, EMBO JOURNAL 11: 3995 (1992).
(
10.1002/j.1460-2075.1992.tb05493.x
) / EMBO JOURNAL (1992) -
HAGAN, I, CLONING AND SEQUENCING OF THE CYCLIN-RELATED CDC13+ GENE AND A CYTOLOGICAL STUDY OF ITS ROLE IN FISSION YEAST MITOSIS, JOURNAL OF CELL SCIENCE 91: 587 (1988).
(
10.1242/jcs.91.4.587
) / JOURNAL OF CELL SCIENCE (1988) -
HARTWELL, L.H., GENETIC-CONTROL OF CELL-DIVISION CYCLE IN YEAST .5. GENETIC ANALYSIS OF CDC MUTANTS, GENETICS 74: 267 (1973).
(
10.1093/genetics/74.2.267
) / GENETICS (1973) -
HARTWELL, L.H., 25 YEARS OF CELL-CYCLE GENETICS, GENETICS 129: 975 (1991).
(
10.1093/genetics/129.4.975
) / GENETICS (1991) 10.1126/science.183.4120.46
-
HINDS, P.W., REGULATION OF RETINOBLASTOMA PROTEIN FUNCTIONS BY ECTOPIC EXPRESSION OF HUMAN CYCLINS, CELL 70: 993 (1992).
(
10.1016/0092-8674(92)90249-C
) / CELL (1992) - HOWE, P.H., TRANSFORMING GROWTH FACTOR-BETA-1 INHIBITION OF P34CDC2 PHOSPHORYLATION AND HISTONE-H1 KINASE-ACTIVITY IS ASSOCIATED WITH G1/S-PHASE GROWTH ARREST, MOLECULAR AND CELLULAR BIOLOGY 11: 1185 (1991). / MOLECULAR AND CELLULAR BIOLOGY (1991)
- HU, Q, THE RETINOBLASTOMA PROTEIN PHYSICALLY ASSOCIATES WITH THE HUMAN CDC2 KINASE, MOLECULAR AND CELLULAR BIOLOGY 12: 971 (1992). / MOLECULAR AND CELLULAR BIOLOGY (1992)
10.1016/0092-8674(91)90236-R
- KITAGAWA, M, CDC2-LIKE KINASE IS ASSOCIATED WITH THE RETINOBLASTOMA PROTEIN, ONCOGENE 7: 1067 (1992). / ONCOGENE (1992)
-
KOFF, A, HUMAN CYCLIN-E, A NEW CYCLIN THAT INTERACTS WITH 2 MEMBERS OF THE CDC2 GENE FAMILY, CELL 66: 1217 (1991).
(
10.1016/0092-8674(91)90044-Y
) / CELL (1991) 10.1126/science.1388288
-
LABBE, J.C., ACTIVATION AT M-PHASE OF A PROTEIN-KINASE ENCODED BY A STARFISH HOMOLOG OF THE CELL-CYCLE CONTROL GENE CDC2+, NATURE 335: 251 (1988).
(
10.1038/335251a0
) / NATURE (1988) -
LAIHO, M, GROWTH-INHIBITION BY TGF-BETA LINKED TO SUPPRESSION OF RETINOBLASTOMA PROTEIN-PHOSPHORYLATION, CELL 62: 175 (1990).
(
10.1016/0092-8674(90)90251-9
) / CELL (1990) -
LEES, E, CYCLIN-E CDK2 AND CYCLIN-A CDK2 KINASES ASSOCIATE WITH P107 AND E2F IN A TEMPORALLY DISTINCT MANNER, GENES & DEVELOPMENT 6: 1874 (1992).
(
10.1101/gad.6.10.1874
) / GENES & DEVELOPMENT (1992) 10.1016/0092-8674(89)90983-5
-
LUDLOW, J.W., THE RETINOBLASTOMA SUSCEPTIBILITY GENE-PRODUCT UNDERGOES CELL CYCLE-DEPENDENT DEPHOSPHORYLATION AND BINDING TO AND RELEASE FROM SV40 LARGE-T, CELL 60: 387 (1990).
(
10.1016/0092-8674(90)90590-B
) / CELL (1990) -
MATSUSHIME, H, IDENTIFICATION AND PROPERTIES OF AN ATYPICAL CATALYTIC SUBUNIT (P34(PSK-J3)/CDK4) FOR MAMMALIAN-D TYPE-G1 CYCLINS, CELL 71: 323 (1992).
(
10.1016/0092-8674(92)90360-O
) / CELL (1992) -
MEYERSON, M, A FAMILY OF HUMAN CDC2-RELATED PROTEIN-KINASES, EMBO JOURNAL 11: 2909 (1992).
(
10.1002/j.1460-2075.1992.tb05360.x
) / EMBO JOURNAL (1992) -
MINSHULL, J, TRANSLATION OF CYCLIN MESSENGER-RNA IS NECESSARY FOR EXTRACTS OF ACTIVATED XENOPUS EGGS TO ENTER MITOSIS, CELL 56: 947 (1989).
(
10.1016/0092-8674(89)90628-4
) / CELL (1989) -
MURRAY, A.W., CYCLIN SYNTHESIS DRIVES THE EARLY EMBRYONIC-CELL CYCLE, NATURE 339: 275 (1989).
(
10.1038/339275a0
) / NATURE (1989) 10.1038/292558a0
10.1038/344503a0
10.1126/science.8384376
-
PAGANO, M, CYCLIN-A IS REQUIRED AT 2 POINTS IN THE HUMAN CELL-CYCLE, EMBO JOURNAL 11: 961 (1992).
(
10.1002/j.1460-2075.1992.tb05135.x
) / EMBO JOURNAL (1992) 10.1126/science.1312258
- PARIS, S, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88: 1029 (1991). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1991)
- PICKHAM, K.M., REQUIREMENT OF MOSXE PROTEIN-KINASE FOR MEIOTIC MATURATION OF XENOPUS OOCYTES INDUCED BY A CDC2 MUTANT LACKING REGULATORY PHOSPHORYLATION SITES, MOLECULAR AND CELLULAR BIOLOGY 12: 3192 (1992). / MOLECULAR AND CELLULAR BIOLOGY (1992)
10.1016/0092-8674(90)90188-K
-
PIGGOTT, J.R., A BIFUNCTIONAL GENE-PRODUCT INVOLVED IN 2 PHASES OF THE YEAST-CELL CYCLE, NATURE 298: 391 (1982).
(
10.1038/298391a0
) / NATURE (1982) -
PINES, J, ISOLATION OF A HUMAN CYCLIN CDNA - EVIDENCE FOR CYCLIN MESSENGER-RNA AND PROTEIN-REGULATION IN THE CELL-CYCLE AND FOR INTERACTION WITH P34-CDC2, CELL 58: 833 (1989).
(
10.1016/0092-8674(89)90936-7
) / CELL (1989) -
PINES, J, MOLECULAR-CLONING AND CHARACTERIZATION OF THE MESSENGER-RNA FOR CYCLIN FROM SEA-URCHIN EGGS, EMBO JOURNAL 6: 2987 (1987).
(
10.1002/j.1460-2075.1987.tb02604.x
) / EMBO JOURNAL (1987) -
PINES, J, HUMAN CYCLIN-A IS ADENOVIRUS E1A-ASSOCIATED PROTEIN-P60 AND BEHAVES DIFFERENTLY FROM CYCLIN-B, NATURE 346: 760 (1990).
(
10.1038/346760a0
) / NATURE (1990) - PINES, J, NEW BIOL 2: 389 (1990). / NEW BIOL (1990)
10.1101/gad.4.1.9
- REED, S.I., MITOTIC ROLE FOR THE CDC28-PROTEIN KINASE OF SACCHAROMYCES-CEREVISIAE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 5697 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
- ROSENBLATT, J, HUMAN CYCLIN-DEPENDENT KINASE-2 IS ACTIVATED DURING THE S-PHASE AND G(2)-PHASE OF THE CELL-CYCLE AND ASSOCIATES WITH CYCLIN-A, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 2824 (1992). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1992)
10.1016/0092-8674(86)90390-9
- SOLOMON, K.J., CELL 63: 1013 (1991). / CELL (1991)
-
SOLOMON, M.J., ROLE OF PHOSPHORYLATION IN P34CDC2 ACTIVATION - IDENTIFICATION OF AN ACTIVATING KINASE, MOLECULAR BIOLOGY OF THE CELL 3: 13 (1992).
(
10.1091/mbc.3.1.13
) / MOLECULAR BIOLOGY OF THE CELL (1992) 10.1016/0092-8674(91)90416-V
-
TSAI, L.H., ISOLATION OF THE HUMAN CDK2 GENE THAT ENCODES THE CYCLIN-A-ASSOCIATED AND ADENOVIRUS-E1A-ASSOCIATED P-33 KINASE, NATURE 353: 174 (1991).
(
10.1038/353174a0
) / NATURE (1991) -
WESTENDORF, J.M., THE ROLE OF CYCLIN-B IN MEIOSIS-I, JOURNAL OF CELL BIOLOGY 108: 1431 (1989).
(
10.1083/jcb.108.4.1431
) / JOURNAL OF CELL BIOLOGY (1989) -
XIONG, Y, D-TYPE CYCLINS ASSOCIATE WITH MULTIPLE PROTEIN-KINASES AND THE DNA-REPLICATION AND REPAIR FACTOR PCNA, CELL 71: 505 (1992).
(
10.1016/0092-8674(92)90518-H
) / CELL (1992) - ZENTELLA, A, TRANSFORMING GROWTH-FACTOR-BETA INDUCES MYOBLAST DIFFERENTIATION IN THE PRESENCE OF MITOGENS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 5176 (1992). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1992)
Dates
Type | When |
---|---|
Created | 18 years, 10 months ago (Oct. 5, 2006, 7:05 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 15, 2024, 6:28 a.m.) |
Indexed | 1 month, 4 weeks ago (July 1, 2025, 9:31 a.m.) |
Issued | 32 years, 4 months ago (April 23, 1993) |
Published | 32 years, 4 months ago (April 23, 1993) |
Published Print | 32 years, 4 months ago (April 23, 1993) |
@article{Koff_1993, title={Negative Regulation of G1 in Mammalian Cells: Inhibition of Cyclin E-Dependent Kinase by TGF-β}, volume={260}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.8475385}, DOI={10.1126/science.8475385}, number={5107}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Koff, Andrew and Ohtsuki, Masahiko and Polyak, Kornelia and Roberts, James M. and Massagué, Joan}, year={1993}, month=apr, pages={536–539} }