title: Lre1 directly inhibits the NDR/Lats kinase Cbk1 at the cell division site in a phosphorylation-dependent manner.
abstract: BACKGROUND
  The nuclear Dbf2 related (NDR) family of protein kinases play important roles in cell-cycle regulation, apoptosis, cell morphogenesis, and development in a variety of organisms. In budding yeast, the NDR kinase complex composed of Cbk1 and its regulatory subunit, Mob2, have an established role in the control of cell separation/abscission that follows cytokinesis. Whereas the activators of Cbk1-Mob2 have been more extensively described, the mechanisms that restrict or inhibit Cbk1-Mob2 catalytic activity remain largely unknown.
  
  
  RESULTS
  We identified the protein Lre1 as a direct inhibitor of Cbk1-Mob2 catalytic activity. We show that Lre1 accumulates at the cell division site in late anaphase and associates with both Mob2 and Cbk1 in vivo and in vitro. Biochemical and functional analysis established that the ability of Lre1 to associate with Cbk1-Mob2 was reduced by mitotic Cdk1 activity and promoted by Cdc14 phosphatase at the end of mitosis. The inhibition of Cbk1-Mob2 by Lre1 was critical to promote the survival of cells lacking the actomyosin driven pathway of cytokinesis.
  
  
  CONCLUSIONS
  We established Lre1 as a direct inhibitor of the NDR kinase Cbk1-Mob2, which is regulated in a cell-cycle-dependent manner. We propose that similar inhibitory proteins may also provide fine tuning for the activity of NDR kinases in other organisms.
authors: Molecular Biology of Centrosomes and Cilia Unit, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors: Ilde
authors: I
authors: Mancini Lombardi
authors: Saravanan
authors: S
authors: Palani
authors: Franz
authors: F
authors: Meitinger
authors: Zoulfia
authors: Z
authors: Darieva
authors: Astrid
authors: A
authors: Hofmann
authors: Andrew D
authors: AD
authors: Sharrocks
authors: Gislene
authors: G
authors: Pereira
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D015536:Down-Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
chemical_list: C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000588849:Lre1 protein, S cerevisiae; C112936:MYO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C423362:CBK1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D018995:Myosin Heavy Chains