Downstream of human NDR kinases: impacting on c-myc and p21 protein stability to control cell cycle progression.
Cell Cycle
; 10(12): 1897-904, 2011 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-21593588
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.
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Bases de datos:
MEDLINE
Asunto principal:
Ciclo Celular
/
Proteínas Proto-Oncogénicas c-myc
/
Proteínas Serina-Treonina Quinasas
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Proteínas Supresoras de Tumor
/
Inhibidor p21 de las Quinasas Dependientes de la Ciclina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Cycle
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suiza