PMID- 11463834
OWN - NLM
STAT- MEDLINE
DCOM- 20010823
LR  - 20240407
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 21
IP  - 16
DP  - 2001 Aug
TI  - The oncoprotein Tax binds the SRC-1-interacting domain of CBP/p300 to mediate 
      transcriptional activation.
PG  - 5520-30
AB  - Oncogenesis associated with human T-cell leukemia virus (HTLV) infection is 
      directly linked to the virally encoded transcription factor Tax. To activate 
      HTLV-1 transcription Tax interacts with the cellular protein CREB and the 
      pleiotropic coactivators CBP and p300. While extensively studied, the molecular 
      mechanisms of Tax transcription function and coactivator utilization are not 
      fully understood. Previous studies have focused on Tax binding to the KIX domain 
      of CBP, as this was believed to be the key step in recruiting the coactivator to 
      the HTLV-1 promoter. In this study, we identify a carboxy-terminal region of CBP 
      (and p300) that strongly interacts with Tax and mediates Tax transcription 
      function. Through deletion mutagenesis, we identify amino acids 2003 to 2212 of 
      CBP, which we call carboxy-terminal region 2 (CR2), as the minimal region for Tax 
      interaction. Interestingly, this domain corresponds to the steroid receptor 
      coactivator 1 (SRC-1)-interacting domain of CBP. We show that a double point 
      mutant targeted to one of the putative alpha-helical motifs in this domain 
      significantly compromises the interaction with Tax. We also characterize the 
      region of Tax responsible for interaction with CR2 and show that the previously 
      identified transactivation domain of Tax (amino acids 312 to 319) participates in 
      CR2 binding. This region of Tax corresponds to a consensus amphipathic helix, and 
      single point mutations targeted to amino acids on the face of this helix abolish 
      interaction with CR2 and dramatically reduce Tax transcription function. Finally, 
      we demonstrate that Tax and SRC-1 bind to CR2 in a mutually exclusive fashion. 
      Together, these studies identify a novel Tax-interacting site on CBP/p300 and 
      extend our understanding of the molecular mechanism of Tax transactivation.
FAU - Scoggin, K E
AU  - Scoggin KE
AD  - Department of Biochemistry and Molecular Biology, Colorado State University, Fort 
      Collins, Colorado 80523, USA.
FAU - Ulloa, A
AU  - Ulloa A
FAU - Nyborg, J K
AU  - Nyborg JK
LA  - eng
GR  - R01 CA055035/CA/NCI NIH HHS/United States
GR  - R01 CA055035-08/CA/NCI NIH HHS/United States
GR  - CA-55035/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Nuclear Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.48 (E1A-Associated p300 Protein)
RN  - EC 2.3.1.48 (Ep300 protein, mouse)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (NCOA1 protein, human)
RN  - EC 2.3.1.48 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
SB  - IM
MH  - Animals
MH  - E1A-Associated p300 Protein
MH  - Escherichia coli
MH  - *Genes, pX
MH  - Histone Acetyltransferases
MH  - Humans
MH  - Mice
MH  - Nuclear Proteins/*genetics
MH  - Nuclear Receptor Coactivator 1
MH  - Recombinant Proteins/genetics
MH  - Trans-Activators/*genetics
MH  - Transcription Factors/genetics
MH  - *Transcriptional Activation
PMC - PMC87274
EDAT- 2001/07/21 10:00
MHDA- 2001/08/24 10:01
PMCR- 2001/08/01
CRDT- 2001/07/21 10:00
PHST- 2001/07/21 10:00 [pubmed]
PHST- 2001/08/24 10:01 [medline]
PHST- 2001/07/21 10:00 [entrez]
PHST- 2001/08/01 00:00 [pmc-release]
AID - 2120 [pii]
AID - 10.1128/MCB.21.16.5520-5530.2001 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2001 Aug;21(16):5520-30. doi: 10.1128/MCB.21.16.5520-5530.2001.