Nuclear translocation of LIM kinase mediates Rho-Rho kinase regulation of cyclin D1 expression

Kristin Roovers, Eric A. Klein, Paola Castagnino, Richard K. Assoian

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

We previously reported that the Rho-Rho kinase pathway controls cyclin D1 expression by preventing its early G1 phase induction in response to Rac and/or Cdc42, thus increasing its dependence on ERK signaling and actin stress fiber formation. We now show that the Rho kinase effector LIM kinase is responsible for this effect. Surprisingly, inhibition of Rac-dependent cyclin D1 expression by LIM kinase is independent of both cofilin phosphorylation and actin polymerization. Instead, specific mutation of its nuclear localization and export sequences showed that LIM kinase acts in the nucleus to suppress Rac/Cdc42-dependent cyclin D1 expression. Our results therefore describe an unexpected role for LIM kinase that requires nuclear translocation. The effect of nuclear LIM kinase on cyclin D1 expression ultimately regulates the duration of G1 phase and the degree to which G1 phase progression depends on actin stress fiber formation and imposition of cellular tension.

Original languageEnglish (US)
Pages (from-to)273-284
Number of pages12
JournalDevelopmental Cell
Volume5
Issue number2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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Lim Kinases
rho-Associated Kinases
Cyclin D1
G1 Phase
Actins
Stress Fibers
Actin Depolymerizing Factors
Phosphorylation
Cell Nucleus Active Transport
Fibers
Polymerization
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Roovers, Kristin ; Klein, Eric A. ; Castagnino, Paola ; Assoian, Richard K. / Nuclear translocation of LIM kinase mediates Rho-Rho kinase regulation of cyclin D1 expression. In: Developmental Cell. 2003 ; Vol. 5, No. 2. pp. 273-284.
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Nuclear translocation of LIM kinase mediates Rho-Rho kinase regulation of cyclin D1 expression. / Roovers, Kristin; Klein, Eric A.; Castagnino, Paola; Assoian, Richard K.

In: Developmental Cell, Vol. 5, No. 2, 01.08.2003, p. 273-284.

Research output: Contribution to journalArticle

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