Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 12 January 1990:
Vol. 247. no. 4939, pp. 205 - 209
DOI: 10.1126/science.2104680
Prev | Table of Contents | Next

Articles

Science, Vol 247, Issue 4939, 205-209
Copyright © 1990 by American Association for the Advancement of Science

articles

Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts

T Seshadri and J Campisi

Department of Biochemistry, Boston University Medical School, MA 02118.

Normal cells in culture invariably undergo senescence, whereby they cease proliferation after a finite number of doublings. Irreversible changes in gene expression occurred in senescent human fetal lung fibroblasts: a non-cell cycle-regulated mRNA was partially repressed; an unusual polyadenylated histone mRNA was expressed; although serum induced c-H-ras, c-myc, and ornithine decarboxylase mRNA normally, ornithine decarboxylase activity was deficient; and serum did not induce mRNA for a replication-dependent histone and for the c-fos proto-oncogene. The loss of c-fos inducibility was the result of a specific, transcriptional block. The results suggest that senescent fibroblasts were unable to proliferate because of, at least in part, selective repression of c-fos; moreover, the multiple changes in gene expression support the view that cellular senescence is a process of terminal differentiation.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Integrin-Linked Kinase Induces Both Senescence-Associated Alterations and Extracellular Fibronectin Assembly in Aging Cardiac Fibroblasts.
X. Chen, Z. Li, Z. Feng, J. Wang, C. Ouyang, W. Liu, B. Fu, G. Cai, C. Wu, R. Wei, et al. (2006)
J. Gerontol. A Biol. Sci. Med. Sci. 61, 1232-1245
   Abstract »    Full Text »    PDF »
Cellular Senescence Impairs Circadian Expression of Clock Genes In Vitro and In Vivo.
T. Kunieda, T. Minamino, T. Katsuno, K. Tateno, J.-i. Nishi, H. Miyauchi, M. Orimo, S. Okada, and I. Komuro (2006)
Circ. Res. 98, 532-539
   Abstract »    Full Text »    PDF »
Developing a Research Agenda in Biogerontology: Basic Mechanisms.
H. R. Warner (2005)
Sci. Aging Knowl. Environ. 2005, pe33
   Abstract »    Full Text »
Loss of Net as Repressor Leads to Constitutive Increased c-fos Transcription in Cervical Cancer Cells.
J. van Riggelen, G. Buchwalter, U. Soto, J. De-Castro Arce, H. z. Hausen, B. Wasylyk, and F. Rosl (2005)
J. Biol. Chem. 280, 3286-3294
   Abstract »    Full Text »    PDF »
Protein Kinase C{delta} Blocks Immediate-Early Gene Expression in Senescent Cells by Inactivating Serum Response Factor.
K. Wheaton and K. Riabowol (2004)
Mol. Cell. Biol. 24, 7298-7311
   Abstract »    Full Text »    PDF »
Mitogen Stimulation Cooperates with Telomere Shortening To Activate DNA Damage Responses and Senescence Signaling.
A. Satyanarayana, R. A. Greenberg, S. Schaetzlein, J. Buer, K. Masutomi, W. C. Hahn, S. Zimmermann, U. Martens, M. P. Manns, and K. L. Rudolph (2004)
Mol. Cell. Biol. 24, 5459-5474
   Abstract »    Full Text »    PDF »
Vintage Gerontology.
I. Chen (2004)
Sci. Aging Knowl. Environ. 2004, nf6-6
   Abstract »    Full Text »
Senescent Phenotype Can Be Reversed by Reduction of Caveolin Status.
K. A. Cho, S. J. Ryu, J. S. Park, I. S. Jang, J. S. Ahn, K. T. Kim, and S. C. Park (2003)
J. Biol. Chem. 278, 27789-27795
   Abstract »    Full Text »    PDF »
An AOA Critical Issue: Aging of the North American Population: New Challenges for Orthopaedics.
J. A. Buckwalter, J. D. Heckman, and D. P. Petrie (2003)
J. Bone Joint Surg. Am. 85, 748-758
   Full Text »    PDF »
Reversal of Senescence in Mouse Fibroblasts through Lentiviral Suppression of p53.
A. M. G. Dirac and R. Bernards (2003)
J. Biol. Chem. 278, 11731-11734
   Abstract »    Full Text »    PDF »
Replicative Senescence Revisited.
R. Marcotte and E. Wang (2002)
J. Gerontol. A Biol. Sci. Med. Sci. 57, B257-269
   Abstract »    Full Text »
Regulation of Collagenase Expression during Replicative Senescence in Human Fibroblasts by Akt-Forkhead Signaling.
M. Mawal-Dewan, A. Lorenzini, L. Frisoni, H. Zhang, V. J. Cristofalo, and C. Sell (2002)
J. Biol. Chem. 277, 7857-7864
   Abstract »    Full Text »    PDF »
Senescence represses the nuclear localization of the serum response factor and differentiation regulates its nuclear localization with lineage specificity.
W Ding, S Gao, and R. Scott (2001)
J. Cell Sci. 114, 1011-1018
   Abstract »    PDF »
Human Papillomavirus Type 16 E7 Oncoprotein Binds and Inactivates Growth-Inhibitory Insulin-Like Growth Factor Binding Protein 3.
B. Mannhardt, S. A. Weinzimer, M. Wagner, M. Fiedler, P. Cohen, P. Jansen-Dürr, and W. Zwerschke (2000)
Mol. Cell. Biol. 20, 6483-6495
   Abstract »    Full Text »
Replicative Senescence and Oxidant-Induced Premature Senescence: Beyond the Control of Cell Cycle Checkpoints.
Q. M. CHEN (2000)
Ann. N.Y. Acad. Sci. 908, 111-125
   Abstract »    Full Text »    PDF »
Human Diploid Fibroblasts Display a Decreased Level of c-fos mRNA at 72 Hours after Exposure to Sublethal H2O2 Stress.
P. DUMONT, M. BURTON, Q. M. CHEN, C. FRIPPIAT, T. PASCAL, J.-F. DIERICK, F. ELIAERS, F. CHAINIAUX, J. REMACLE, and O. TOUSSAINT (2000)
Ann. N.Y. Acad. Sci. 908, 306-309
   Full Text »    PDF »
Age-dependent increase in c-fos activity and cyclin A expression in vascular smooth muscle cells: A potential link between aging, smooth muscle cell proliferation and atherosclerosis.
A. Rivard, N. Principe, and V. Andres (2000)
Cardiovasc Res 45, 1026-1034
   Abstract »    Full Text »    PDF »
Microinjection of Anti-p21 Antibodies Induces Senescent Hs68 Human Fibroblasts to Synthesize DNA but not To Divide.
Y. Ma, S. A. Prigent, T. L. Born, C. R. Monell, J. R. Feramisco, and B. L. Bertolaet (1999)
Cancer Res. 59, 5341-5348
   Abstract »    Full Text »    PDF »
Transformation Blocks Differentiation-induced Inhibition of Serum Response Factor Interactions with Serum Response Elements.
W. Ding, M. M. Witte, and R. E. Scott (1999)
Cancer Res. 59, 3795-3802
   Abstract »    Full Text »    PDF »
Age-dependent atrophy and microgravity travel: what do they have in common?.
E. WANG (1999)
FASEB J 13, 167-174
   Abstract »    Full Text »    PDF »
Expression of Catalytically Active Telomerase Does Not Prevent Premature Senescence Caused by Overexpression of Oncogenic Ha-Ras in Normal Human Fibroblasts.
S. Wei, W. Wei, and J. M. Sedivy (1999)
Cancer Res. 59, 1539-1543
   Abstract »    Full Text »    PDF »
Aging and the cornea.
R G A FARAGHER, B MULHOLLAND, S J TUFT, S SANDEMAN, and P T KHAW (1997)
Br. J. Ophthalmol. 81, 814-817
   Full Text »    PDF »
Selective Alteration of Long-Term Potentiation-Induced Transcriptional Response in Hippocampus of Aged, Memory-Impaired Rats.
A. Lanahan, G. Lyford, G. S. Stevenson, P. F. Worley, and C. A. Barnes (1997)
J. Neurosci. 17, 2876-2885
   Abstract »    Full Text »    PDF »
1,25-Dihydroxyvitamin D3 Induction of Nerve Growth Factor in L929 Mouse Fibroblasts: Effect of Vitamin D Receptor Regulation and Potency of Vitamin D3 Analogs.
I. M. Musiol and D. Feldman (1997)
Endocrinology 138, 12-18
   Abstract »    Full Text »    PDF »
SV40 Large T Antigen Transactivates the Human cdc2 Promoter by Inducing a CCAAT Box Binding Factor.
H. Chen, J. Campisi, and R. Padmanabhan (1996)
J. Biol. Chem. 271, 13959-13967
   Abstract »    Full Text »    PDF »
A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development.
B. Barres, M. Lazar, and M. Raff (1994)
Development 120, 1097-1108
   Abstract »    PDF »
Deregulation of cyclins D1 and E and suppression of cdk2 and cdk4 in senescent human fibroblasts.
F. Lucibello, A Sewing, S Brusselbach, C Burger, and R Muller (1993)
J. Cell Sci. 105, 123-133
   Abstract »    PDF »
Senescence of nickel-transformed cells by an X chromosome: possible epigenetic control.
C. Klein, K Conway, X. Wang, R. Bhamra, X. Lin, M. Cohen, L Annab, J. Barrett, and M Costa (1991)
Science 251, 796-799
   Abstract »    PDF »
Gerontology research comes of age.
A Gibbons (1990)
Science 250, 622-625
   PDF »
Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer.
J. Maier, P Voulalas, D Roeder, and T Maciag (1990)
Science 249, 1570-1574
   Abstract »    PDF »
Replicative senescence: the human fibroblast comes of age.
S Goldstein (1990)
Science 249, 1129-1133
   Abstract »    PDF »
Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts.
G. Stein, M Beeson, and L Gordon (1990)
Science 249, 666-669
   Abstract »    PDF »
Up-regulation of Caveolin Attenuates Epidermal Growth Factor Signaling in Senescent Cells.
W.-Y. Park, J.-S. Park, K.-A Cho, D.-I. Kim, Y.-G. Ko, J.-S. Seo, and S. C. Park (2000)
J. Biol. Chem. 275, 20847-20852
   Abstract »    Full Text »    PDF »
Significance of Nuclear Relocalization of ERK1/2 in Reactivation of c-fos Transcription and DNA Synthesis in Senescent Fibroblasts.
J.-r. Kim-Kaneyama, K. Nose, and M. Shibanuma (2000)
J. Biol. Chem. 275, 20685-20692
   Abstract »    Full Text »    PDF »
Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging.
A. Krtolica, S. Parrinello, S. Lockett, P.-Y. Desprez, and J. Campisi (2001)
PNAS 98, 12072-12077
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)