Mechanoregulation of proliferation

Xiaogang Jiang, Paul F. Austin, Robert A. Niederhoff, Scott R. Manson, Jacob J. Riehm, Brian L. Cook, Gina Pengue, Kanchan Chitaley, Keiko Nakayama, Keiichi I. Nakayama, Steven J. Weintraub

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The proliferation of all nontransformed adherent cells is dependent upon the development of mechanical tension within the cell; however, little is known about the mechanisms by which signals regulated by mechanical tension are integrated with those regulated by growth factors. We show here that Skp2, a component of a ubiquitin ligase complex that mediates the degradation of several proteins that inhibit proliferation, is upregulated when increased mechanical tension develops in intact smooth muscle and that its upregulation is critical for the smooth muscle proliferative response to increased mechanical tension. Notably, whereas growth factors regulate Skp2 at the level of protein stability, we found that mechanical tension regulates Skp2 at the transcriptional level. Importantly, we demonstrate that the calcium-regulated transcription factor NFATc1 is a critical mediator of the effect of increased mechanical tension on Skp2 transcription. These findings identify Skp2 as a node at which signals from mechanical tension and growth factors are integrated to regulate proliferation, and they define calcium-NFAT-Skp2 signaling as a critical pathway in the mechanoregulation of proliferation.

Original languageEnglish
Pages (from-to)5104-5114
Number of pages11
JournalMolecular and cellular biology
Volume29
Issue number18
DOIs
Publication statusPublished - 2009 Sep

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Jiang, X., Austin, P. F., Niederhoff, R. A., Manson, S. R., Riehm, J. J., Cook, B. L., Pengue, G., Chitaley, K., Nakayama, K., Nakayama, K. I., & Weintraub, S. J. (2009). Mechanoregulation of proliferation. Molecular and cellular biology, 29(18), 5104-5114. https://doi.org/10.1128/MCB.00465-09