A Novel Role of Annexin A2 in Human Type i Collagen Gene Expression

4Citations
Citations of this article
11Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The fibrillar collagen scaffold of the extracellular matrix provides a structural framework for cells in tissues and regulates intercellular communication; its disregulation has been associated with tumour development and progression. Previous work has shown that expression of type I collagen, the most abundant mammalian extracellular matrix protein, is decreased in chemically or virally transformed cells. This negative regulation could be mapped to a proximal COL1A2 promoter element spanning a CME (Collagen Modulating Element) site in SV40-transformed human fibroblasts (SV-WI38) that binds an unknown repressing protein. By magnetic bead pull-down, we observed a multi-protein complex bound to the CME with preference for single-stranded over conventional double-stranded DNA. MALDI-TOF mass spectrometry of the CME-binding protein complex revealed involvement of nuclear annexin A2 (AnxA2) which was increased in SV40-transformed cells. Further EMSA analysis demonstrated that AnxA2 did not directly bind to the DNA but stabilised the complex and led to an increase in protein binding to the CME in SV-WI38 but not untransformed WI38 cells. Knockdown of AnxA2 by siRNA increased type I collagen production in both WI38 and SV-WI38 cells; however, these effects were not mediated at the transcriptional level. Rather, our data indicate a novel functional role of AnxA2 in the negative post-transcriptional regulation of type I collagen synthesis in human fibroblasts. In SV40-transformed cells, AnxA2 is accumulated at the proximal COL1A2 promoter region, suggesting close association with the transcriptional machinery that possibly facilitates binding to the emerging mRNA, eventually contributing to overall repression of type I collagen protein synthesis. J. Cell. Biochem. 116: 408-417, 2015.

Cite

CITATION STYLE

APA

Schäfer, G., Hitchcock, J. K., Shaw, T. M., Katz, A. A., & Parker, M. I. (2015). A Novel Role of Annexin A2 in Human Type i Collagen Gene Expression. Journal of Cellular Biochemistry, 116(3), 408–417. https://doi.org/10.1002/jcb.24989

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free