Journal
CELL CYCLE
Volume 10, Issue 12, Pages 1897-1904Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.10.12.15826
Keywords
NDR/LATS kinase family; NDR1; NDR2; STK38; STK38L; MST kinases; MST3; HIPPO; p21; c-myc
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Funding
- Swiss Cancer League
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The mammalian genome encodes 4 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.
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