PMID- 21245298
OWN - NLM
STAT- MEDLINE
DCOM- 20110323
LR  - 20211203
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 108
IP  - 5
DP  - 2011 Feb 1
TI  - Differential regulation of the p73 cistrome by mammalian target of rapamycin 
      reveals transcriptional programs of mesenchymal differentiation and 
      tumorigenesis.
PG  - 2076-81
LID - 10.1073/pnas.1011936108 [doi]
AB  - The transcription factor p73 plays critical roles during development and 
      tumorigenesis. It exhibits sequence identity and structural homology with p53, 
      and can engage p53-like tumor-suppressive programs. However, different pathways 
      regulate p53 and p73, and p73 is not mutated in human tumors. Therefore, p73 
      represents a therapeutic target, and there is a critical need to understand genes 
      and noncoding RNAs regulated by p73 and how they change during treatment 
      regimens. Here, we define the p73 genomic binding profile and demonstrate its 
      modulation by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) and 
      inducer of p73. Rapamycin selectively increased p73 occupancy at a subset of its 
      binding sites. In addition, multiple determinants of p73 binding, activity, and 
      function were evident, and were modulated by mTOR. We generated an mTOR-p73 
      signature that is enriched for p73 target genes and miRNAs that are involved in 
      mesenchymal differentiation and tumorigenesis, can classify rhabdomyosarcomas by 
      clinical subtype, and can predict patient outcome.
FAU - Rosenbluth, Jennifer M
AU  - Rosenbluth JM
AD  - Department of Biochemistry, Center in Molecular Toxicology, and Division of 
      Cancer Biostatistics, Department of Biostatistics, Vanderbilt-Ingram Cancer 
      Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
FAU - Mays, Deborah J
AU  - Mays DJ
FAU - Jiang, Aixiang
AU  - Jiang A
FAU - Shyr, Yu
AU  - Shyr Y
FAU - Pietenpol, Jennifer A
AU  - Pietenpol JA
LA  - eng
SI  - GEO/GSE15719
GR  - GM07347/GM/NIGMS NIH HHS/United States
GR  - R01 CA105436/CA/NCI NIH HHS/United States
GR  - R01 CA070856/CA/NCI NIH HHS/United States
GR  - T32 GM007347/GM/NIGMS NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - ES00267/ES/NIEHS NIH HHS/United States
GR  - P30 ES000267/ES/NIEHS NIH HHS/United States
GR  - CA105436/CA/NCI NIH HHS/United States
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - CA70856/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110118
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Nuclear Proteins)
RN  - 0 (TP73 protein, human)
RN  - 0 (Tumor Protein p73)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Cell Transformation, Neoplastic
MH  - DNA-Binding Proteins/*genetics/metabolism
MH  - Genome, Human
MH  - Humans
MH  - Mesoderm/*pathology
MH  - MicroRNAs/genetics
MH  - Nuclear Proteins/*genetics/metabolism
MH  - Protein Binding
MH  - Rhabdomyosarcoma/classification/genetics/pathology
MH  - TOR Serine-Threonine Kinases/*genetics
MH  - *Transcription, Genetic
MH  - Tumor Protein p73
MH  - Tumor Suppressor Proteins/*genetics/metabolism
PMC - PMC3033306
COIS- The authors declare no conflict of interest.
EDAT- 2011/01/20 06:00
MHDA- 2011/03/24 06:00
PMCR- 2011/08/01
CRDT- 2011/01/20 06:00
PHST- 2011/01/20 06:00 [entrez]
PHST- 2011/01/20 06:00 [pubmed]
PHST- 2011/03/24 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - 1011936108 [pii]
AID - 201011936 [pii]
AID - 10.1073/pnas.1011936108 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2076-81. doi: 
      10.1073/pnas.1011936108. Epub 2011 Jan 18.