© The Rockefeller University Press,
0021-9525/1998//1427 $5.00
The Journal of Cell Biology, Volume 140, Number 6,
, 1998 1427-1439
A Requirement for Cyclin D3–Cyclin-dependent Kinase (cdk)-4 Assembly in the Cyclic Adenosine Monophosphate–dependent Proliferation of Thyrocytes
Fabienne Depoortere*,
Alexandra Van Keymeulen*,
Jiri Lukas
,
Sabine Costagliola*,
Jirina Bartkova
,
Jacques E. Dumont*,
Jiri Bartek
,
Pierre P. Roger*, and
Sarah Dremier*
* Institute of Interdisciplinary Research, Université Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium; and
Division of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark
In different systems, cyclic adenosine monophosphate (cAMP) either blocks or promotes cell cycle progression in mid to late G1 phase. Dog thyroid epithelial cells in primary culture constitute a model of positive control of DNA synthesis initiation and G0-S prereplicative phase progression by cAMP as a second messenger for thyrotropin (TSH). The cAMP-dependent mitogenic pathway is unique as it is independent of mitogen-activated protein kinase activation and differs from growth factor–dependent pathways at the level of the expression of several protooncogenes/transcription factors. This study examined the involvement of D-type G1 cyclins and their associated cyclin-dependent kinase (cdk4) in the cAMP-dependent G1 phase progression of dog thyroid cells. Unlike epidermal growth factor (EGF)+serum and other cAMP-independent mitogens, TSH did not induce the accumulation of cyclins D1 and D2 and partially inhibited the basal expression of the most abundant cyclin D3. However, TSH stimulation enhanced the nuclear detection of cyclin D3. This effect correlated with G1 and S phase progression. It was found to reflect both the unmasking of an epitope of cyclin D3 close to its domain of interaction with cdk4, and the nuclear translocation of cyclin D3. TSH and EGF+serum also induced a previously undescribed nuclear translocation of cdk4, the assembly of precipitable cyclin D3–cdk4 complexes, and the Rb kinase activity of these complexes. Previously, cdk4 activity was found to be required in the cAMP-dependent mitogenic pathway of dog thyrocytes, as in growth factor pathways. Here, microinjections of a cyclin D3 antibody showed that cyclin D3 is essential in the TSH/ cAMP-dependent mitogenesis, but not in the pathway of growth factors that induce cyclins D1 and D2. The present study (a) provides the first example in a normal cell of a stimulation of G1 phase progression occurring independently of an enhanced accumulation of cyclins D, (b) identifies the activation of cyclin D3 and cdk4 through their enhanced assembly and/or nuclear translocation, as first convergence steps of the parallel cAMP-dependent and growth factor mitogenic pathways, and (c) strongly suggests that this new mechanism is essential in the cAMP-dependent mitogenesis, which provides the first direct demonstration of the requirement for cyclin D3 in a G1 phase progression.
Abbreviations used in this paper: BrdU, 8-bromo-deoxyuridine; cdk, cyclin-dependent kinase; HGF, hepatocyte growth factor; TPA, 12-O-tetradecanoylphorbol 13-acetate; TSH, thyrotropin.
Address all correspondence to Pierre Roger, IRIBHN, Campus Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium. Tel.: 322 555 41 53. Fax: 322 555 46 55.
The first two authors made equal contributions to this work.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Bockstaele, L., Bisteau, X., Paternot, S., Roger, P. P.
(2009). Differential Regulation of Cyclin-Dependent Kinase 4 (CDK4) and CDK6, Evidence that CDK4 Might Not Be Activated by CDK7, and Design of a CDK6 Activating Mutation. Mol. Cell. Biol.
29: 4188-4200
[Abstract]
[Full Text]
-
Rocha, A. S., Paternot, S., Coulonval, K., Dumont, J. E., Soares, P., Roger, P. P.
(2008). Cyclic AMP Inhibits the Proliferation of Thyroid Carcinoma Cell Lines through Regulation of CDK4 Phosphorylation. Mol. Biol. Cell
19: 4814-4825
[Abstract]
[Full Text]
-
Fukushima, T., Nedachi, T., Akizawa, H., Akahori, M., Hakuno, F., Takahashi, S.-I.
(2008). Distinct Modes of Activation of Phosphatidylinositol 3-Kinase in Response to Cyclic Adenosine 3', 5'-Monophosphate or Insulin-Like Growth Factor I Play Different Roles in Regulation of Cyclin D1 and p27Kip1 in FRTL-5 Cells. Endocrinology
149: 3729-3742
[Abstract]
[Full Text]
-
Dremier, S., Milenkovic, M., Blancquaert, S., Dumont, J. E., Doskeland, S. O., Maenhaut, C., Roger, P. P.
(2007). Cyclic Adenosine 3',5'-Monophosphate (cAMP)-Dependent Protein Kinases, But Not Exchange Proteins Directly Activated by cAMP (Epac), Mediate Thyrotropin/cAMP-Dependent Regulation of Thyroid Cells. Endocrinology
148: 4612-4622
[Abstract]
[Full Text]
-
Costa, M. J., Senou, M., Van Rode, F., Ruf, J., Capello, M., Dequanter, D., Lothaire, P., Dessy, C., Dumont, J. E., Many, M.-C., Van Sande, J.
(2007). Reciprocal Negative Regulation between Thyrotropin/3',5'-Cyclic Adenosine Monophosphate-Mediated Proliferation and Caveolin-1 Expression in Human and Murine Thyrocytes. Mol. Endocrinol.
21: 921-932
[Abstract]
[Full Text]
-
Paternot, S., Dumont, J. E., Roger, P. P.
(2006). Differential Utilization of Cyclin D1 and Cyclin D3 in the Distinct Mitogenic Stimulations by Growth Factors and TSH of Human Thyrocytes in Primary Culture. Mol. Endocrinol.
20: 3279-3292
[Abstract]
[Full Text]
-
Bockstaele, L., Kooken, H., Libert, F., Paternot, S., Dumont, J. E., de Launoit, Y., Roger, P. P., Coulonval, K.
(2006). Regulated Activating Thr172 Phosphorylation of Cyclin-Dependent Kinase 4(CDK4): Its Relationship with Cyclins and CDK "Inhibitors".. Mol. Cell. Biol.
26: 5070-5085
[Abstract]
[Full Text]
-
Fortemaison, N., Blancquaert, S., Dumont, J. E., Maenhaut, C., Aktories, K., Roger, P. P., Dremier, S.
(2005). Differential Involvement of the Actin Cytoskeleton in Differentiation and Mitogenesis of Thyroid Cells: Inactivation of Rho Proteins Contributes to Cyclic Adenosine Monophosphate-Dependent Gene Expression but Prevents Mitogenesis. Endocrinology
146: 5485-5495
[Abstract]
[Full Text]
-
Mitsutake, N., Knauf, J. A., Mitsutake, S., Mesa, C. Jr., Zhang, L., Fagin, J. A.
(2005). Conditional BRAFV600E Expression Induces DNA Synthesis, Apoptosis, Dedifferentiation, and Chromosomal Instability in Thyroid PCCL3 Cells. Cancer Res.
65: 2465-2473
[Abstract]
[Full Text]
-
Lewis, A. E., Fikaris, A. J., Prendergast, G. V., Meinkoth, J. L.
(2004). Thyrotropin and Serum Regulate Thyroid Cell Proliferation through Differential Effects on p27 Expression and Localization. Mol. Endocrinol.
18: 2321-2332
[Abstract]
[Full Text]
-
Paternot, S., Coulonval, K., Dumont, J. E., Roger, P. P.
(2003). Cyclic AMP-dependent Phosphorylation of Cyclin D3-bound CDK4 Determines the Passage through the Cell Cycle Restriction Point in Thyroid Epithelial Cells. J. Biol. Chem.
278: 26533-26540
[Abstract]
[Full Text]
-
Tamamori-Adachi, M., Ito, H., Sumrejkanchanakij, P., Adachi, S., Hiroe, M., Shimizu, M., Kawauchi, J., Sunamori, M., Marumo, F., Kitajima, S., Ikeda, M.-A.
(2003). Critical Role of Cyclin D1 Nuclear Import in Cardiomyocyte Proliferation. Circ. Res.
92
: e12-e19
[Abstract]
[Full Text]
-
Dumont, J. E., Dremier, S., Pirson, I., Maenhaut, C.
(2002). Cross signaling, cell specificity, and physiology. Am. J. Physiol. Cell Physiol.
283: C2-C28
[Abstract]
[Full Text]
-
Dolci, S., Pellegrini, M., Di Agostino, S., Geremia, R., Rossi, P.
(2001). Signaling through Extracellular Signal-regulated Kinase Is Required for Spermatogonial Proliferative Response to Stem Cell Factor. J. Biol. Chem.
276: 40225-40233
[Abstract]
[Full Text]
-
Kimura, T., Van Keymeulen, A., Golstein, J., Fusco, A., Dumont, J. E., Roger, P. P.
(2001). Regulation of Thyroid Cell Proliferation by TSH and Other Factors: A Critical Evaluation of in Vitro Models. Endocr. Rev.
22: 631-656
[Abstract]
[Full Text]
-
Van Keymeulen, A., Deleu, S., Bartek, J., Dumont, J. E., Roger, P. P.
(2001). Respective Roles of Carbamylcholine and Cyclic Adenosine Monophosphate in Their Synergistic Regulation of Cell Cycle in Thyroid Primary Cultures. Endocrinology
142: 1251-1259
[Abstract]
[Full Text]
-
Swan, A., Hijal, S., Hilfiker, A., Suter, B.
(2001). Identification of New X-Chromosomal Genes Required for Drosophila Oogenesis and Novel Roles for fs(1)Yb, brainiac and dunce. Genome Res
11: 67-77
[Abstract]
[Full Text]
-
Jones, C. J., Kipling, D., Morris, M., Hepburn, P., Skinner, J., Bounacer, A., Wyllie, F. S., Ivan, M., Bartek, J., Wynford-Thomas, D., Bond, J. A.
(2000). Evidence for a Telomere-Independent "Clock" Limiting RAS Oncogene-Driven Proliferation of Human Thyroid Epithelial Cells. Mol. Cell. Biol.
20: 5690-5699
[Abstract]
[Full Text]
-
Gabriella De Vita, , Berlingieri, M. T., Visconti, R., Castellone, M. D., Viglietto, G., Baldassarre, G., Zannini, M., Bellacosa, A., Tsichlis, P. N., Fusco, A., Santoro, M.
(2000). Akt/Protein Kinase B Promotes Survival and Hormone-independent Proliferation of Thyroid Cells in the Absence of Dedifferentiating and Transforming Effects. Cancer Res.
60: 3916-3920
[Abstract]
[Full Text]
-
Depoortere, F., Pirson, I., Bartek, J., Dumont, J. E., Roger, P. P.
(2000). Transforming Growth Factor beta 1 Selectively Inhibits the Cyclic AMP-dependent Proliferation of Primary Thyroid Epithelial Cells by Preventing the Association of Cyclin D3-cdk4 with Nuclear p27kip1. Mol. Biol. Cell
11: 1061-1076
[Abstract]
[Full Text]
-
Feliciello, A., Gallo, A., Mele, E., Porcellini, A., Troncone, G., Garbi, C., Gottesman, M. E., Avvedimento, E. V.
(2000). The Localization and Activity of cAMP-dependent Protein Kinase Affect Cell Cycle Progression in Thyroid Cells. J. Biol. Chem.
275: 303-311
[Abstract]
[Full Text]
-
Tanguay, D., Pavlovic, S., Piatelli, M. J., Bartek, J., Chiles, T. C.
(1999). B Cell Antigen Receptor-Mediated Activation of Cyclin-Dependent Retinoblastoma Protein Kinases and Inhibition by Co-Cross-Linking with Fc{gamma} Receptors. J. Immunol.
163: 3160-3168
[Abstract]
[Full Text]
-
Taules, M., Rodriguez-Vilarrupla, A., Rius, E., Estanyol, J. M., Casanovas, O., Sacks, D. B., Perez-Paya, E., Bachs, O., Agell, N.
(1999). Calmodulin Binds to p21Cip1 and Is Involved in the Regulation of Its Nuclear Localization. J. Biol. Chem.
274: 24445-24448
[Abstract]
[Full Text]
-
Pestell, R. G., Albanese, C., Reutens, A. T., Segall, J. E., Lee, R. J., Arnold, A.
(1999). The Cyclins and Cyclin-Dependent Kinase Inhibitors in Hormonal Regulation of Proliferation and Differentiation. Endocr. Rev.
20: 501-534
[Abstract]
[Full Text]