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Downstream of human NDR kinases: impacting on c-myc and p21 protein stability to control cell cycle progression.

Abstract
The mammalian genome encodes four members of the NDR/LATS kinase family: NDR1 (STK38), NDR2 (STK38L), LATS1 and LATS2, which are highly conserved from yeast to man. Members of the NDR/LATS kinase family have been implicated in a variety of biological processes ranging from cell division and morphology to apoptosis and tumor suppression. In mammals, LATS1/2 function as central parts of the HIPPO tumor suppressor pathway by restricting the activity of the YAP/TAZ proto-oncogenes. Recent evidence suggested that NDR1/2 are also part of an extended HIPPO tumor suppressor pathway. Apart from functions in apoptosis signaling and tumor suppression, NDR1/2 have been implicated in controlling centrosome duplication and mitotic chromosome alignment downstream of the HIPPO kinase homologs MST1 and MST2. Significantly, we also reported recently that NDR1/2 are controlling G 1/S transition downstream of a third MST family member MST3. Intriguingly, this newly described MST3-NDR1/2 axis promotes G 1 progression by stabilizing c-myc and preventing p21 accumulation, indicating a potential pro-tumorigenic role for NDR kinases. Here, we discuss these novel cell cycle functions of NDR kinases in a broader context and elaborate on possible explanations for the opposing functions of NDR kinases in normal and tumor biology.
AuthorsHauke Cornils, Reto S Kohler, Alexander Hergovich, Brian A Hemmings
JournalCell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 10 Issue 12 Pg. 1897-904 (Jun 15 2011) ISSN: 1551-4005 [Electronic] United States
PMID21593588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Proteins
  • LATS1 protein, human
  • LATS2 protein, human
  • Protein-Serine-Threonine Kinases
  • STK38 protein, human
  • STK38L protein, human
Topics
  • Animals
  • Cell Cycle
  • Cyclin-Dependent Kinase Inhibitor p21 (physiology)
  • Humans
  • Protein Stability
  • Protein-Serine-Threonine Kinases (physiology)
  • Proto-Oncogene Proteins c-myc (physiology)
  • Tumor Suppressor Proteins (physiology)

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