Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP.

Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP. Research Abstract Details 

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Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP. Abstract Text:

Yawei Hao,Alex Chun,Kevin Cheung,Babak Rashidi,Xiaolong Yang,

LATS (large tumor suppressor) or warts is a Ser/Thr kinase that belongs to the Ndr/LATS subfamily of AGC (protein kinase A/PKG/PKC) kinases. It is a tumor suppressor gene originally isolated from Drosophila and recently isolated from mice and humans. Drosophila or mice mutant for LATS develop tumors in various tissues. Recent studies in Drosophila demonstrate that LATS is a central player of an emerging tumor suppressor pathway called the Hippo-LATS/Warts pathway that suppresses tumor growth by regulating cell proliferation, cell growth, and cell death. Although tremendous progress has been made toward understanding the roles of LATS in tumorigenesis, the kinase substrates of LATS or downstream target proteins mediating LATS function remain largely unknown. In this study, we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. We have also identified HX(R/H/K)XX(S/T) as the consensus phosphorylation sequence for LATS/Ndr kinase substrates. Significantly, we have discovered that LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. Finally, by using microarray analysis, we have also identified many oncogenes or tumor suppressor genes up-regulated or down-regulated by YAP. These research findings will have profound impacts on our understanding of the molecular mechanism of the LATS tumor suppressor and the emerging Hippo-LATS/Warts pathway.

Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP. Publishing Authors By Initials

Y Hao,A Chun,K Cheung,B Rashidi,X Yang,

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Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of biological chemistry

VOLUME: 283

Page Numbers: 5496-509

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 24

MONTH: 12

YEAR: 2007

Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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Grant and Affiliation Information for Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP.

AFFILIATION: Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario K7L 3N6, Canada.

Country: United States

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MEDLINETA: J Biol Chem

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