title: MOZ-TIF2 repression of nuclear receptor-mediated transcription requires multiple domains in MOZ and in the CID domain of TIF2.
abstract: BACKGROUND
  Fusion of the MOZ and TIF2 genes by an inv (8) (p11q13) translocation has been identified in patients with acute mixed-lineage leukemia. Characterization of the molecular structure of the MOZ-TIF2 fusion protein suggested that the fusion protein would effect on nuclear receptor signaling.
  
  
  RESULTS
  A series of deletions from the N-terminus of the MOZ-TIF2 fusion protein demonstrated that the MOZ portion is essential for nuclear localization of the fusion protein. Transient expression of MOZ-TIF2 dramatically decreased both basal and estradiol inducible reporter gene activity in an estrogen receptor element (ERE) driven luciferase reporter system and decreased androgen-inducible reporter gene activity in an androgen receptor element (ARE) luciferase reporter system. Deletions in the MOZ portion of the MOZ-TIF2 fusion protein reduced the suppression in the ER reporter system. Stable expression of MOZ-TIF2 inhibited retinoic acid (RA) inducible endogenous CD11b and C/EBPbeta gene response. The suppression of the reporter systems was released with either a CID domain deletion or with mutations of leucine-rich repeats in the TIF2 portion of MOZ-TIF2. The co-expression of TIF2, but not CBP, with MOZ-TIF2 partially restored the inhibition of the reporter systems. In addition, analysis of protein interactions demonstrated MOZ-TIF2 interaction with the C-terminus of CBP through both the MOZ and TIF2 portions of the fusion protein.
  
  
  CONCLUSIONS
  MOZ-TIF2 inhibited nuclear receptor-mediated gene response by aberrant recruitment of CBP and both the MOZ and TIF2 portions are required for this inhibition.
authors: Feist-Weiller Cancer Center and Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, USA. hyin@lsuhsc.edu
authors: Hong
authors: H
authors: Yin
authors: Jonathan
authors: J
authors: Glass
authors: Kerry L
authors: KL
authors: Blanchard
mesh_terms: D000208:Acute Disease; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone; D017930:Genes, Reporter; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D015514:Oncogene Proteins, Fusion; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human; D003345:Corticosterone
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