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Science 19 July 1996:
Vol. 273. no. 5273, pp. 359 - 361
DOI: 10.1126/science.273.5273.359
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Reports

Resistance to Apoptosis Conferred by Cdk Inhibitors During Myocyte Differentiation

Jian Wang and Kenneth Walsh *

Proliferating murine C2C12 myoblasts can undergo either terminal differentiation or programmed cell death under conditions of mitogen deprivation. Unlike myoblasts, differentiated myotubes were resistant to apoptosis. During myogenesis the appearance of the apoptosis-resistant phenotype was correlated with the induction of the cyclin-dependent kinase (Cdk) inhibitor p21CIP1 but not with the appearance of myogenin, a marker expressed earlier in differentiation. Forced expression of the Cdk inhibitors p21CIP1 or p16INK4A blocked apoptosis during myocyte differentiation. These data indicate that induction of Cdk inhibitors may serve to protect differentiating myocytes from programmed cell death as well as play a role in establishing the postmitotic state.

Division of Cardiovascular Research, St. Elizabeth's Medical Center and Tufts University School of Medicine, Boston, MA 02135, USA.
* To whom correspondence should be addressed.


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Direct Involvement of N-Cadherin-mediated Signaling in Muscle Differentiation.
P. Goichberg and B. Geiger (1998)
Mol. Biol. Cell 9, 3119-3131
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Serum or Growth Factor Deprivation Induces the Expression of Alkaline Phosphatase in Human Gingival Fibroblasts.
T. Abe, Y. Hara, Y. Abe, Y. Aida, and K. Maeda (1998)
Journal of Dental Research 77, 1700-1707
   Abstract »    PDF »
A Matter of Life and Cell Death.
G. Evan and T. Littlewood (1998)
Science 281, 1317-1322
   Abstract »    Full Text »
Transcriptional Activation of the p21WAF1,CIP1,SDI1 Gene by Interleukin-6 Type Cytokines. A PREREQUISITE FOR THEIR PRO-DIFFERENTIATING AND ANTI-APOPTOTIC EFFECTS ON HUMAN OSTEOBLASTIC CELLS.
T. Bellido, C. A. O'Brien, P. K. Roberson, and S. C. Manolagas (1998)
J. Biol. Chem. 273, 21137-21144
   Abstract »    Full Text »    PDF »
Arresting developments in the cardiac myocyte cell cycle: Role of cyclin-dependent kinase inhibitors.
G. Brooks, R. A Poolman, and J.-M. Li (1998)
Cardiovasc Res 39, 301-311
   Abstract »    Full Text »    PDF »
Bcl-2 Expression Identifies an Early Stage of Myogenesis and Promotes Clonal Expansion of Muscle Cells.
J. A. Dominov, J. J. Dunn, and J. B. Miller (1998)
J. Cell Biol. 142, 537-544
   Abstract »    Full Text »    PDF »
Antisense telomerase treatment: induction of two distinct pathways, apoptosis and differentiation.
S. Kondo, Y. Tanaka, Y. Kondo, M. Hitomi, G. H. Barnett, Y. Ishizaka, J. Liu, T. Haqqi, A. Nishiyama, B. Villeponteau, et al. (1998)
FASEB J 12, 801-811
   Abstract »    Full Text »
Regulation of p21(WAF1) Expression During Normal Myeloid Differentiation.
R. A. Steinman, J. Huang, B. Yaroslavskiy, J. P. Goff, E. D. Ball, and A. Nguyen (1998)
Blood 91, 4531-4542
   Abstract »    Full Text »    PDF »
Caspase-dependent activation of cyclin-dependent kinases during Fas-induced apoptosis in Jurkat cells.
B.-B. Zhou, H. Li, J. Yuan, and M. W. Kirschner (1998)
PNAS 95, 6785-6790
   Abstract »    Full Text »    PDF »
Phosphorylation and Inhibition of Rat Glucocorticoid Receptor Transcriptional Activation by Glycogen Synthase Kinase-3 (GSK-3). SPECIES-SPECIFIC DIFFERENCES BETWEEN HUMAN AND RAT GLUCOCORTICOID RECEPTOR SIGNALING AS REVEALED THROUGH GSK-3 PHOSPHORYLATION.
I. Rogatsky, C. L. M. Waase, and M. J. Garabedian (1998)
J. Biol. Chem. 273, 14315-14321
   Abstract »    Full Text »    PDF »
The Activity of Differentiation Factors Induces Apoptosis in Polyomavirus Large T-Expressing Myoblasts.
G. M. Fimia, V. Gottifredi, B. Bellei, M. R. Ricciardi, A. Tafuri, P. Amati, and R. Maione (1998)
Mol. Biol. Cell 9, 1449-1463
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The basic helix-loop-helix protein BETA2 interacts with p300 to coordinate differentiation of secretin-expressing enteroendocrine cells.
H. Mutoh, F. J. Naya, M.-J. Tsai, and A. B. Leiter (1998)
Genes & Dev. 12, 820-830
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Developmental remodeling and shortening of the cardiac outflow tract involves myocyte programmed cell death.
M Watanabe, A Choudhry, M Berlan, A Singal, E Siwik, S Mohr, and S. Fisher (1998)
Development 125, 3809-3820
   Abstract »    PDF »
Mouse myoblasts can fuse and form a normal sarcomere in the absence of beta1 integrin expression.
E Hirsch, L Lohikangas, D Gullberg, S Johansson, and R Fassler (1998)
J. Cell Sci. 111, 2397-2409
   Abstract »    PDF »
Reversal of myogenic terminal differentiation by SV40 large T antigen results in mitosis and apoptosis.
T Endo and B Nadal-Ginard (1998)
J. Cell Sci. 111, 1081-1093
   Abstract »    PDF »
Cell heterogeneity upon myogenic differentiation: down-regulation of MyoD and Myf-5 generates 'reserve cells'.
N Yoshida, S Yoshida, K Koishi, K Masuda, and Y Nabeshima (1998)
J. Cell Sci. 111, 769-779
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Inhibition of Growth of Human Vascular Smooth Muscle Cells by Overexpression of p21 Gene Through Induction of Apoptosis.
H. Matsushita, R. Morishita, I. Kida, M. Aoki, S.-i. Hayashi, N. Tomita, K. Yamamoto, A. Moriguchi, A. Noda, Y. Kaneda, et al. (1998)
Hypertension 31, 493-498
   Abstract »    Full Text »    PDF »


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