PMID- 17974916
OWN - NLM
STAT- MEDLINE
DCOM- 20080108
LR  - 20240104
IS  - 0890-9369 (Print)
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Linking)
VI  - 21
IP  - 21
DP  - 2007 Nov 1
TI  - Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact 
      inhibition and tissue growth control.
PG  - 2747-61
AB  - The Hippo pathway plays a key role in organ size control by regulating cell 
      proliferation and apoptosis in Drosophila. Although recent genetic studies have 
      shown that the Hippo pathway is regulated by the NF2 and Fat tumor suppressors, 
      the physiological regulations of this pathway are unknown. Here we show that in 
      mammalian cells, the transcription coactivator YAP (Yes-associated protein), is 
      inhibited by cell density via the Hippo pathway. Phosphorylation by the Lats 
      tumor suppressor kinase leads to cytoplasmic translocation and inactivation of 
      the YAP oncoprotein. Furthermore, attenuation of this phosphorylation of YAP or 
      Yorkie (Yki), the Drosophila homolog of YAP, potentiates their growth-promoting 
      function in vivo. Moreover, YAP overexpression regulates gene expression in a 
      manner opposite to cell density, and is able to overcome cell contact inhibition. 
      Inhibition of YAP function restores contact inhibition in a human cancer cell 
      line bearing deletion of Salvador (Sav), a Hippo pathway component. 
      Interestingly, we observed that YAP protein is elevated and nuclear localized in 
      some human liver and prostate cancers. Our observations demonstrate that YAP 
      plays a key role in the Hippo pathway to control cell proliferation in response 
      to cell contact.
FAU - Zhao, Bin
AU  - Zhao B
AD  - Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
FAU - Wei, Xiaomu
AU  - Wei X
FAU - Li, Weiquan
AU  - Li W
FAU - Udan, Ryan S
AU  - Udan RS
FAU - Yang, Qian
AU  - Yang Q
FAU - Kim, Joungmok
AU  - Kim J
FAU - Xie, Joe
AU  - Xie J
FAU - Ikenoue, Tsuneo
AU  - Ikenoue T
FAU - Yu, Jindan
AU  - Yu J
FAU - Li, Li
AU  - Li L
FAU - Zheng, Pan
AU  - Zheng P
FAU - Ye, Keqiang
AU  - Ye K
FAU - Chinnaiyan, Arul
AU  - Chinnaiyan A
FAU - Halder, Georg
AU  - Halder G
FAU - Lai, Zhi-Chun
AU  - Lai ZC
FAU - Guan, Kun-Liang
AU  - Guan KL
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yki protein, Drosophila)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (wts protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (hpo protein, Drosophila)
SB  - IM
MH  - 14-3-3 Proteins/metabolism
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Communication/genetics
MH  - Cell Count
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Contact Inhibition/*genetics
MH  - Drosophila/genetics/growth & development
MH  - Drosophila Proteins/*antagonists & inhibitors/chemistry/metabolism/*physiology
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Models, Biological
MH  - NIH 3T3 Cells
MH  - Nuclear Proteins/*antagonists & inhibitors/chemistry/metabolism/*physiology
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/*physiology
MH  - Protein Transport
MH  - Signal Transduction/physiology
MH  - Trans-Activators/*antagonists & inhibitors/chemistry/metabolism/*physiology
MH  - YAP-Signaling Proteins
PMC - PMC2045129
EDAT- 2007/11/03 09:00
MHDA- 2008/01/09 09:00
PMCR- 2008/05/01
CRDT- 2007/11/03 09:00
PHST- 2007/11/03 09:00 [pubmed]
PHST- 2008/01/09 09:00 [medline]
PHST- 2007/11/03 09:00 [entrez]
PHST- 2008/05/01 00:00 [pmc-release]
AID - 21/21/2747 [pii]
AID - 10.1101/gad.1602907 [doi]
PST - ppublish
SO  - Genes Dev. 2007 Nov 1;21(21):2747-61. doi: 10.1101/gad.1602907.