tailieunhanh - Báo cáo khoa học: UXT interacts with the transcriptional repressor protein EVI1 and suppresses cell transformation

The EVI1 transcriptional repressor is critical to the normal development of a variety of tissues and participates in the progression of acute myeloid leu-kaemias. The repressor domain (Rp) was used to screen an adult human kidney yeast two-hybrid library and a novel binding partner designated ubiquitously expressed transcript (UXT) was isolated. | ễFEBS Journal UXT interacts with the transcriptional repressor protein EVI1 and suppresses cell transformation Roger McGilvray1 Mark Walker2 and Chris Bartholomew1 1 Department of Biological BiomedicalSciences Glasgow Caledonian University UK 2 CRUK Beatson Laboratories Beatson Institute for Cancer Research Glasgow UK Keywords ART-27 cell transformation EVI1 leukemia ubiquitously expressed transcript Correspondence C. Bartholomew Glasgow Caledonian University Department of Biological Biomedical Sciences City Campus Cowcaddens Road Glasgow G4 OBA UK Fax 44 0 141 331 3208 Tel 44 0 141 331 3213 E-mail Received 30 June 2006 revised 10 May 2007 accepted 8 June 2007 doi The EVI1 transcriptional repressor is critical to the normal development of a variety of tissues and participates in the progression of acute myeloid leukaemias. The repressor domain Rp was used to screen an adult human kidney yeast two-hybrid library and a novel binding partner designated ubiquitously expressed transcript UXT was isolated. Enforced expression of UXT in Evi1-expressing Rat1 fibroblasts suppresses cell transformation and UXT may therefore be a negative regulator of Evi1 biological activity. The Rp-binding site for UXT was determined and non-UXT-binding Evi1 mutants Evi1D706-707 were developed which retain the ability to bind the corepressor mCtBP2. Evi1D706-707 transforms Rat1 fibroblasts showing that the interaction is not essential for Evi1-mediated cell transformation. However Evi1D706-707 produces an increased proportion of large colonies relative to wild-type showing that endogenous UXT has an inhibitory effect on Evi1 biological activity. Exogenous UXT still suppresses Evi1D706-707-mediated cell transformation indicating that it inhibits cell proliferation and or survival by both Evi1-dependent and Evi1-independ-ent mechanisms. These observations are consistent with the growthsuppressive function attributed to UXT in human .