This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Benanti, J. A.
Right arrow Articles by Galloway, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Benanti, J. A.
Right arrow Articles by Galloway, D. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2002, p. 7385-7397, Vol. 22, No. 21
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.21.7385-7397.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Induction of Extracellular Matrix-Remodeling Genes by the Senescence-Associated Protein APA-1

Jennifer A. Benanti,1,2 Dawnnica K. Williams,1,2 Kristin L. Robinson,1 Harvey L. Ozer,3 and Denise A. Galloway1*

Program in Cancer Biology, Fred Hutchinson Cancer Research Center,1 Molecular and Cellular Biology Graduate Program, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, Washington,2 Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey3

Received 12 March 2002/ Returned for modification 13 May 2002/ Accepted 11 July 2002

Human fibroblasts undergo cellular senescence after a finite number of divisions, in response to the erosion of telomeres. In addition to being terminally arrested in the cell cycle, senescent fibroblasts express genes that are normally induced upon wounding, including genes that remodel the extracellular matrix. We have identified the novel zinc finger protein APA-1, whose expression increased in senescent human fibroblasts independent of telomere shortening. Extended passage, telomerase-immortalized fibroblasts had increased levels of APA-1 as well as the cyclin-dependent kinase inhibitor p16. In fibroblasts, APA-1 was modified by the ubiquitin-like protein SUMO-1, which increased APA-1 half-life, possibly by blocking ubiquitin-mediated degradation. Overexpression of APA-1 did not cause cell cycle arrest; but, it induced transcription of the extracellular matrix-remodeling genes MMP1 and PAI2, which are associated with fibroblast senescence. MMP1 and PAI2 transcript levels also increased in telomerase-immortalized fibroblasts that had high levels of APA-1, demonstrating that the matrix-remodeling phenotype of senescent fibroblasts was not induced by telomere attrition alone. APA-1 was able to transactivate and bind to the MMP1 promoter, suggesting that APA-1 is a transcription factor that regulates expression of matrix-remodeling genes during fibroblast senescence.

* Corresponding author. Mailing address: Program in Cancer Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024. Phone: (206) 667-4500. Fax: (206) 667-5815. E-mail: dgallowa{at}fhcrc.org.

Molecular and Cellular Biology, November 2002, p. 7385-7397, Vol. 22, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.21.7385-7397.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Benanti, J. A., Wang, M. L., Myers, H. E., Robinson, K. L., Grandori, C., Galloway, D. A. (2007). Epigenetic Down-Regulation of ARF Expression Is a Selection Step in Immortalization of Human Fibroblasts by c-Myc. Mol Cancer Res 5: 1181-1189 [Abstract] [Full Text]  
  • Kidd, M., Nadler, B., Mane, S., Eick, G., Malfertheiner, M., Champaneria, M., Pfragner, R., Modlin, I. (2007). GeneChip, geNorm, and gastrointestinal tumors: novel reference genes for real-time PCR. Physiol. Genomics 30: 363-370 [Abstract] [Full Text]  
  • Zhang, X., Kim, J., Ruthazer, R., McDevitt, M. A., Wazer, D. E., Paulson, K. E., Yee, A. S. (2006). The HBP1 Transcriptional Repressor Participates in RAS-Induced Premature Senescence. Mol. Cell. Biol. 26: 8252-8266 [Abstract] [Full Text]  
  • Bevilacqua, M. A., Iovine, B., Zambrano, N., D'Ambrosio, C., Scaloni, A., Russo, T., Cimino, F. (2005). Fibromodulin Gene Transcription Is Induced by Ultraviolet Irradiation, and Its Regulation Is Impaired in Senescent Human Fibroblasts. J. Biol. Chem. 280: 31809-31817 [Abstract] [Full Text]  
  • Gurkan, C., Lapp, H., Alory, C., Su, A. I., Hogenesch, J. B., Balch, W. E. (2005). Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome. Mol. Biol. Cell 16: 3847-3864 [Abstract] [Full Text]  
  • Benanti, J. A., Galloway, D. A. (2004). Normal Human Fibroblasts Are Resistant to RAS-Induced Senescence. Mol. Cell. Biol. 24: 2842-2852 [Abstract] [Full Text]  
  • Yerlikaya, A., Stanley, B. A. (2004). S-Adenosylmethionine Decarboxylase Degradation by the 26 S Proteasome Is Accelerated by Substrate-mediated Transamination. J. Biol. Chem. 279: 12469-12478 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»