title: Cellular contractility requires ubiquitin mediated proteolysis.
abstract: BACKGROUND
  Cellular contractility, essential for cell movement and proliferation, is regulated by microtubules, RhoA and actomyosin. The RhoA dependent kinase ROCK ensures the phosphorylation of the regulatory Myosin II Light Chain (MLC) Ser19, thereby activating actomyosin contractions. Microtubules are upstream inhibitors of contractility and their depolymerization or depletion cause cells to contract by activating RhoA. How microtubule dynamics regulates RhoA remains, a major missing link in understanding contractility.
  
  
  RESULTS
  We observed that contractility is inhibited by microtubules not only, as previously reported, in adherent cells, but also in non-adhering interphase and mitotic cells. Strikingly we observed that contractility requires ubiquitin mediated proteolysis by a Cullin-RING ubiquitin ligase. Inhibition of proteolysis, ubiquitination and neddylation all led to complete cessation of contractility and considerably reduced MLC Ser19 phosphorylation.
  
  
  CONCLUSIONS
  Our results imply that cells express a contractility inhibitor that is degraded by ubiquitin mediated proteolysis, either constitutively or in response to microtubule depolymerization. This degradation seems to depend on a Cullin-RING ubiquitin ligase and is required for cellular contractions.
authors: The Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel.
authors: Yuval
authors: Y
authors: Cinnamon
authors: Oren
authors: O
authors: Feine
authors: Helfrid
authors: H
authors: Hochegger
authors: Alexander
authors: A
authors: Bershadsky
authors: Michael
authors: M
authors: Brandeis
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D006868:Hydrolysis; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010766:Phosphorylation; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D025801:Ubiquitin; D009219:Myosin-Light-Chain Kinase