PMID- 18158288
OWN - NLM
STAT- MEDLINE
DCOM- 20080415
LR  - 20220330
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 9
DP  - 2008 Feb 29
TI  - Tumor suppressor LATS1 is a negative regulator of oncogene YAP.
PG  - 5496-509
AB  - 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.
FAU - Hao, Yawei
AU  - Hao Y
AD  - Department of Pathology and Molecular Medicine, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Chun, Alex
AU  - Chun A
FAU - Cheung, Kevin
AU  - Cheung K
FAU - Rashidi, Babak
AU  - Rashidi B
FAU - Yang, Xiaolong
AU  - Yang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071224
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (HEMGN protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YY1AP1 protein, human)
RN  - 0 (Yap1 protein, mouse)
RN  - EC 2.7.1.- (LATS1 protein, human)
RN  - EC 2.7.1.- (Lats1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (hpo protein, Drosophila)
SB  - IM
MH  - Active Transport, Cell Nucleus/genetics
MH  - Adaptor Proteins, Signal Transducing/genetics/metabolism
MH  - Amino Acid Motifs/genetics
MH  - Animals
MH  - Cell Cycle Proteins
MH  - Cell Nucleus/genetics/*metabolism
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic/genetics/*metabolism
MH  - Drosophila
MH  - Drosophila Proteins/genetics/metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Mice
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Oncogene Proteins/genetics/*metabolism
MH  - Phosphoproteins/genetics/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcription, Genetic/genetics
MH  - Tumor Suppressor Proteins/genetics/*metabolism
MH  - YAP-Signaling Proteins
EDAT- 2007/12/26 09:00
MHDA- 2008/04/16 09:00
CRDT- 2007/12/26 09:00
PHST- 2007/12/26 09:00 [pubmed]
PHST- 2008/04/16 09:00 [medline]
PHST- 2007/12/26 09:00 [entrez]
AID - S0021-9258(20)57270-0 [pii]
AID - 10.1074/jbc.M709037200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Feb 29;283(9):5496-509. doi: 10.1074/jbc.M709037200. Epub 2007 
      Dec 24.