PMID- 10393185
OWN - NLM
STAT- MEDLINE
DCOM- 19990831
LR  - 20201209
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 13
DP  - 1999 Jul 1
TI  - The Pax3-FKHR oncoprotein is unresponsive to the Pax3-associated repressor hDaxx.
PG  - 3702-11
AB  - The Pax3-FKHR fusion protein is present in alveolar rhabdomyosarcoma and results 
      from the t(2;13) (q35;q14) chromosomal translocation. Its oncogenic activity is
      dependent on a combination of protein-DNA and protein-protein interactions
      mediated by the Pax3 homeodomain recognition helix. In this report we demonstrate
      that human Daxx (hDaxx) interacts with Pax3 in vivo and with DNA-bound Pax3 in
      vitro. This interaction is mediated primarily through the homeodomain recognition
      helix with the additional involvement of the octapeptide domain and its
      N-terminal flanking amino acids. Through this interaction hDaxx represses the
      transcriptional activity of Pax3 by approximately 80%. The Pax3-FKHR fusion is
      unresponsive to this repressive effect despite an observed endogenous interaction
      with hDaxx in a rhabdomyosarcoma tumor cell line. Therefore, these data support
      the model that fusion of FKHR to Pax3 not only adds a strong transactivation
      domain, but also deregulates transcriptional control of Pax3 by overriding the
      natural repressive effect of hDaxx.
FAU - Hollenbach, A D
AU  - Hollenbach AD
AD  - Departments of Genetics, St Jude Children's Research Hospital, 332 North
      Lauderdale, Memphis, TN 38105, USA.
FAU - Sublett, J E
AU  - Sublett JE
FAU - McPherson, C J
AU  - McPherson CJ
FAU - Grosveld, G
AU  - Grosveld G
LA  - eng
GR  - CA-21765/CA/NCI NIH HHS/United States
GR  - CA71907-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Co-Repressor Proteins)
RN  - 0 (DAXX protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Daxx protein, mouse)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (PAX3 Transcription Factor)
RN  - 0 (PAX3 protein, human)
RN  - 0 (Paired Box Transcription Factors)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 138016-91-8 (Pax3 protein, mouse)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Carrier Proteins/chemistry/genetics/isolation & purification/*metabolism
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Co-Repressor Proteins
MH  - DNA/genetics/metabolism
MH  - DNA-Binding Proteins/chemistry/*metabolism
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Molecular Chaperones
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - *Nuclear Proteins
MH  - Oncogene Proteins, Fusion/chemistry/*metabolism
MH  - PAX3 Transcription Factor
MH  - Paired Box Transcription Factors
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Repressor Proteins/chemistry/genetics/isolation & purification/*metabolism
MH  - Rhabdomyosarcoma/genetics
MH  - Sequence Deletion
MH  - Transcription Factors/*metabolism
MH  - Transfection
MH  - Translocation, Genetic/genetics
MH  - Yeasts/genetics
PMC - PMC1171447
EDAT- 1999/07/07 00:00
MHDA- 1999/07/07 00:01
CRDT- 1999/07/07 00:00
PHST- 1999/07/07 00:00 [pubmed]
PHST- 1999/07/07 00:01 [medline]
PHST- 1999/07/07 00:00 [entrez]
AID - 10.1093/emboj/18.13.3702 [doi]
PST - ppublish
SO  - EMBO J. 1999 Jul 1;18(13):3702-11. doi: 10.1093/emboj/18.13.3702.