Human smooth muscle α-actin gene is a transcriptional target of the p53 tumor suppressor protein

Katherine A. Comer, Phillip A. Dennis, Lydia Armstrong, Joseph J. Catino, Michael B. Kastan, C. Chandra Kumar

Research output: Contribution to journalArticle

Abstract

Smooth muscle (sm) α-actin is expressed in vascular smooth muscle cells and fibroblast cells. Its expression is regulated by cell proliferation and repressed during oncogenic transformation. In this study, we demonstrate that p53 activation is associated with a dramatic increase in organized microfilament bundles and an increase in sm α-actin mRNA level. Wild-type p53, but not mutant p53, strongly stimulated human sm α-actin promoter activity in p53 null cell lines. The sequences homologous to the p53 consensus sequence and to the p53 binding sequence from the muscle creatine kinase were found within a specific region of the sm α-actin promoter. This sequence was sufficient to confer p53-dependent activation to a heterologous promoter and p53 was capable of binding to this sequence as assessed by gel shift analysis. Ionizing irradiation of colorectal tumor cells caused an increase in α-actin mRNA level in a p53-dependent manner. Taken together, these results demonstrate that human sm actin gene is a transcriptional target for p53 tumor suppressor protein and represents the first example of a cytoskeletal gene with a functionally defined p53 response element.

Original languageEnglish (US)
Pages (from-to)1299-1308
Number of pages10
JournalOncogene
Volume16
Issue number10
StatePublished - Mar 12 1998

Fingerprint

Tumor Suppressor Protein p53
Smooth Muscle
Actins
Genes
MM Form Creatine Kinase
Null Lymphocytes
Messenger RNA
Consensus Sequence
Response Elements
Electrophoretic Mobility Shift Assay
Sequence Homology
Actin Cytoskeleton
Vascular Smooth Muscle
Smooth Muscle Myocytes
Colorectal Neoplasms
Fibroblasts
Cell Proliferation
Cell Line

Keywords

  • α-actin
  • Cytoskeleton
  • p53
  • Transactivation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Comer, K. A., Dennis, P. A., Armstrong, L., Catino, J. J., Kastan, M. B., & Kumar, C. C. (1998). Human smooth muscle α-actin gene is a transcriptional target of the p53 tumor suppressor protein. Oncogene, 16(10), 1299-1308.

Human smooth muscle α-actin gene is a transcriptional target of the p53 tumor suppressor protein. / Comer, Katherine A.; Dennis, Phillip A.; Armstrong, Lydia; Catino, Joseph J.; Kastan, Michael B.; Kumar, C. Chandra.

In: Oncogene, Vol. 16, No. 10, 12.03.1998, p. 1299-1308.

Research output: Contribution to journalArticle

Comer, KA, Dennis, PA, Armstrong, L, Catino, JJ, Kastan, MB & Kumar, CC 1998, 'Human smooth muscle α-actin gene is a transcriptional target of the p53 tumor suppressor protein', Oncogene, vol. 16, no. 10, pp. 1299-1308.
Comer KA, Dennis PA, Armstrong L, Catino JJ, Kastan MB, Kumar CC. Human smooth muscle α-actin gene is a transcriptional target of the p53 tumor suppressor protein. Oncogene. 1998 Mar 12;16(10):1299-1308.
Comer, Katherine A. ; Dennis, Phillip A. ; Armstrong, Lydia ; Catino, Joseph J. ; Kastan, Michael B. ; Kumar, C. Chandra. / Human smooth muscle α-actin gene is a transcriptional target of the p53 tumor suppressor protein. In: Oncogene. 1998 ; Vol. 16, No. 10. pp. 1299-1308.
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