PMID- 17889654
OWN - NLM
STAT- MEDLINE
DCOM- 20071101
LR  - 20211203
IS  - 0092-8674 (Print)
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Linking)
VI  - 130
IP  - 6
DP  - 2007 Sep 21
TI  - Elucidation of a universal size-control mechanism in Drosophila and mammals.
PG  - 1120-33
AB  - Coordination of cell proliferation and cell death is essential to attain proper 
      organ size during development and for maintaining tissue homeostasis throughout 
      postnatal life. In Drosophila, these two processes are orchestrated by the Hippo 
      kinase cascade, a growth-suppressive pathway that ultimately antagonizes the 
      transcriptional coactivator Yorkie (Yki). Here we demonstrate that a single 
      phosphorylation site in Yki mediates the growth-suppressive output of the Hippo 
      pathway. Hippo-mediated phosphorylation inactivates Yki by excluding it from the 
      nucleus, whereas loss of Hippo signaling leads to nuclear accumulation and 
      therefore increased Yki activity. We further delineate a mammalian Hippo 
      signaling pathway that culminates in the phosphorylation of YAP, the mammalian 
      homolog of Yki. Using a conditional YAP transgenic mouse model, we demonstrate 
      that the mammalian Hippo pathway is a potent regulator of organ size, and that 
      its dysregulation leads to tumorigenesis. These results uncover a universal 
      size-control mechanism in metazoan.
FAU - Dong, Jixin
AU  - Dong J
AD  - Department of Molecular Biology and Genetics, Johns Hopkins University School of 
      Medicine, Baltimore, MD 21205, USA.
FAU - Feldmann, Georg
AU  - Feldmann G
FAU - Huang, Jianbin
AU  - Huang J
FAU - Wu, Shian
AU  - Wu S
FAU - Zhang, Nailing
AU  - Zhang N
FAU - Comerford, Sarah A
AU  - Comerford SA
FAU - Gayyed, Mariana F
AU  - Gayyed MF
FAU - Anders, Robert A
AU  - Anders RA
FAU - Maitra, Anirban
AU  - Maitra A
FAU - Pan, Duojia
AU  - Pan D
LA  - eng
GR  - R01 CA113669-01/CA/NCI NIH HHS/United States
GR  - K08 DK067187/DK/NIDDK NIH HHS/United States
GR  - R01 CA113669-04/CA/NCI NIH HHS/United States
GR  - R01CA113669/CA/NCI NIH HHS/United States
GR  - R01 CA113669-02/CA/NCI NIH HHS/United States
GR  - DK067187/DK/NIDDK NIH HHS/United States
GR  - EY015708/EY/NEI NIH HHS/United States
GR  - R01 CA113669-05/CA/NCI NIH HHS/United States
GR  - R21DK072532/DK/NIDDK NIH HHS/United States
GR  - R21 DK072532/DK/NIDDK NIH HHS/United States
GR  - R01 CA113669-03/CA/NCI NIH HHS/United States
GR  - R01 EY015708/EY/NEI NIH HHS/United States
GR  - R01 CA113669/CA/NCI NIH HHS/United States
GR  - R01 DK081417/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (LAT2 protein, human)
RN  - 0 (Large Neutral Amino Acid-Transporter 1)
RN  - 0 (Nuclear Proteins)
RN  - 0 (SAV1 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YY1AP1 protein, human)
RN  - 0 (Yki protein, Drosophila)
RN  - 452VLY9402 (Serine)
RN  - 80168379AG (Doxorubicin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (wts protein, Drosophila)
RN  - EC 2.7.1.11 (STK4 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (STK3 protein, human)
RN  - EC 2.7.11.1 (Serine-Threonine Kinase 3)
RN  - EC 2.7.11.1 (hpo protein, Drosophila)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - *Apoptosis
MH  - Cell Cycle Proteins/metabolism
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - *Cell Proliferation
MH  - Cytoplasm/metabolism
MH  - Doxorubicin
MH  - Drosophila/cytology/enzymology/genetics/*growth & development/metabolism
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Homeostasis
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Large Neutral Amino Acid-Transporter 1/metabolism
MH  - Liver Neoplasms, Experimental/chemically induced/enzymology/metabolism/pathology
MH  - Mammals/*growth & development/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Mutation
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Organ Size
MH  - Phosphorylation
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Serine/metabolism
MH  - Serine-Threonine Kinase 3
MH  - *Signal Transduction
MH  - Trans-Activators/genetics/*metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Transfection
MH  - YAP-Signaling Proteins
PMC - PMC2666353
MID - NIHMS97880
EDAT- 2007/09/25 09:00
MHDA- 2007/11/02 09:00
PMCR- 2009/04/07
CRDT- 2007/09/25 09:00
PHST- 2007/04/02 00:00 [received]
PHST- 2007/06/11 00:00 [revised]
PHST- 2007/07/16 00:00 [accepted]
PHST- 2007/09/25 09:00 [pubmed]
PHST- 2007/11/02 09:00 [medline]
PHST- 2007/09/25 09:00 [entrez]
PHST- 2009/04/07 00:00 [pmc-release]
AID - S0092-8674(07)00956-7 [pii]
AID - 10.1016/j.cell.2007.07.019 [doi]
PST - ppublish
SO  - Cell. 2007 Sep 21;130(6):1120-33. doi: 10.1016/j.cell.2007.07.019.