PMID- 19749760
OWN - NLM
STAT- MEDLINE
DCOM- 20091014
LR  - 20211020
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Linking)
VI  - 41
IP  - 10
DP  - 2009 Oct
TI  - Polyhomeotic has a tumor suppressor activity mediated by repression of Notch 
      signaling.
PG  - 1076-82
LID - 10.1038/ng.414 [doi]
AB  - Polycomb Group (PcG) proteins silence critical developmental genes and modulate 
      cell proliferation. Using the Drosophila melanogaster eye as a model system, we 
      show that cells with mutations in the gene locus (ph) that encodes the PcG 
      protein Polyhomeotic (PH) overproliferate and lose both the ability to 
      differentiate and their normal polarity. They invade the neighboring tissues and, 
      when combined with an activated form of the Ras proto-oncogene, they trigger the 
      formation of metastases. PcG proteins bind to multiple genes in the Notch pathway 
      and control their transcription as well as Notch signaling. The massive 
      cell-autonomous overproliferation of ph mutant cell clones can be rescued by 
      ectopic expression of a dominant negative form of Notch or by RNA interference 
      (RNAi)-mediated repression of Notch. Conversely, overexpression of ph induces a 
      small-eye phenotype that is rescued by activation of Notch signaling. These data 
      show that ph is a tumor suppressor locus that controls cellular proliferation by 
      silencing multiple Notch signaling components.
FAU - Martinez, Anne-Marie
AU  - Martinez AM
AD  - Institut de Genetique Humaine, Centre Nationale de la Recherche Scientifique, 
      Montpellier, France.
FAU - Schuettengruber, Bernd
AU  - Schuettengruber B
FAU - Sakr, Samy
AU  - Sakr S
FAU - Janic, Ana
AU  - Janic A
FAU - Gonzalez, Cayetano
AU  - Gonzalez C
FAU - Cavalli, Giacomo
AU  - Cavalli G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090913
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (N protein, Drosophila)
RN  - 0 (Nucleoproteins)
RN  - 0 (Receptors, Notch)
RN  - 0 (ph-d protein, Drosophila)
RN  - EC 2.3.2.27 (Polycomb Repressive Complex 1)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Polarity
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic/genetics/metabolism/pathology
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Drosophila melanogaster/cytology/genetics/growth & development/*metabolism
MH  - Eye/cytology/metabolism
MH  - Genes, Tumor Suppressor
MH  - Microscopy, Electron, Scanning
MH  - Mutation
MH  - Nucleoproteins/genetics/*metabolism
MH  - Polycomb Repressive Complex 1
MH  - RNA Interference
MH  - Receptors, Notch/genetics/*metabolism
MH  - *Signal Transduction
EDAT- 2009/09/15 06:00
MHDA- 2009/10/15 06:00
CRDT- 2009/09/15 06:00
PHST- 2009/04/02 00:00 [received]
PHST- 2009/06/05 00:00 [accepted]
PHST- 2009/09/15 06:00 [entrez]
PHST- 2009/09/15 06:00 [pubmed]
PHST- 2009/10/15 06:00 [medline]
AID - ng.414 [pii]
AID - 10.1038/ng.414 [doi]
PST - ppublish
SO  - Nat Genet. 2009 Oct;41(10):1076-82. doi: 10.1038/ng.414. Epub 2009 Sep 13.