Mammalian sterile 20-like kinases in tumor suppression: an emerging pathway.

Emerging evidence suggests that the proapoptotic kinase mammalian sterile 20-like kinase 2 (MST2) acts in a novel tumor suppression pathway. Recently, we showed that Raf-1 kinase sequesters and inhibits MST2 and that this event is critical for Raf-mediated cell survival. In this review, we summarize Raf control of MST2 and we outline a novel pathway involving the downstream effector proteins Salvador and Warts/Lats that may act to limit the positive effects of Raf-mitogen-activated protein kinase signaling in cancer cells.

[1]  Chun Xing Li,et al.  Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3 , 2000, Nature Genetics.

[2]  Norinobu M. Watanabe,et al.  The Ste20 group kinases as regulators of MAP kinase cascades. , 2001, Trends in cell biology.

[3]  W. Tao,et al.  Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction , 1999, Nature Genetics.

[4]  W. Kolch.  Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. , 2000, The Biochemical journal.

[5]  E. Wagner,et al.  Embryonic lethality and fetal liver apoptosis in mice lacking the c‐raf‐1 gene , 2001, The EMBO journal.

[6]  R. Erikson,et al.  Newly identified stress-responsive protein kinases, Krs-1 and Krs-2. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[7]  E. Nigg,et al.  The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1 , 2005, Oncogene.

[8]  C. Pritchard,et al.  MEK kinase activity is not necessary for Raf‐1 function , 2001, The EMBO journal.

[9]  Sung-Hee Ahn,et al.  Sterile 20 Kinase Phosphorylates Histone H2B at Serine 10 during Hydrogen Peroxide-Induced Apoptosis in S. cerevisiae , 2005, Cell.

[10]  R. Buchsbaum,et al.  Cell Signaling: Life or Death Decisions of Ras Proteins , 2002, Current Biology.

[11]  R. Xavier,et al.  The Scaffold Protein CNK1 Interacts with the Tumor Suppressor RASSF1A and Augments RASSF1A-induced Cell Death* , 2004, Journal of Biological Chemistry.

[12]  Su Jeong Song,et al.  The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC–Cdc20 complex , 2004, Nature Cell Biology.

[13]  W. Kolch,et al.  Taming the Hippo: Raf-1 Controls Apoptosis by Suppressing MST2/Hippo , 2005, Cell cycle.

[14]  W. Tao,et al.  Lats2, a putative tumor suppressor, inhibits G1/S transition , 2003, Oncogene.

[15]  W. Kolch,et al.  Conferring specificity on the ubiquitous Raf/MEK signalling pathway , 2004, British Journal of Cancer.

[16]  R. Xavier,et al.  Identification of a Novel Ras-Regulated Proapoptotic Pathway , 2002, Current Biology.

[17]  A. MacKenzie,et al.  The inhibitors of apoptosis (IAPs) and their emerging role in cancer , 1998, Oncogene.

[18]  Walter Kolch,et al.  Role of the Kinase MST2 in Suppression of Apoptosis by the Proto-Oncogene Product Raf-1 , 2004, Science.

[19]  K. Katagiri,et al.  RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1 , 2003, Nature Immunology.

[20]  E. Krebs,et al.  Caspase‐mediated activation and induction of apoptosis by the mammalian Ste20‐like kinase Mst1 , 1998, The EMBO journal.

[21]  W. Tao,et al.  LATS1 tumor suppressor regulates G2/M transition and apoptosis , 2002, Oncogene.

[22]  J. Minna,et al.  Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours , 2001, Oncogene.

[23]  B. Hay,et al.  Coupling cell growth, proliferation, and death. Hippo weighs in. , 2003, Developmental cell.

[24]  Mathew J Garnett,et al.  Guilty as charged: B-RAF is a human oncogene. , 2004, Cancer cell.

[25]  Jonathan Chernoff,et al.  Apoptotic Phosphorylation of Histone H2B Is Mediated by Mammalian Sterile Twenty Kinase , 2003, Cell.