Tcl protein functions as an inhibitor of de novo DNA…蛋白作为从头的抑制剂.pdfVIP

Tcl1 protein functions as an inhibitor of de novo DNA methylation in B-cell chronic lymphocytic leukemia (CLL) a a a a a a Alexey Palamarchuk , Pearlly S. Yan , Nicola Zanesi , Linan Wang , Benjamin Rodrigues , Mark Murphy , Veronica Balattia a a a b b , Arianna Bottoni , Natalya Nazaryan , Hansjuerg Alder , Laura Rassenti , Thomas J. Kipps , Michael Freitasa, Carlo M. Crocea,1, and Yuri Pekarskya,1 aHuman Cancer Genetics Program and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University School of Medicine, Columbus, OH 43210; and bDepartment of Medicine, University of California at San Diego, La Jolla, CA 92093 Contributed by Carlo M. Croce, January 3, 2012 (sent for review December 1, 2011) B-cell chronic lymphocytic leukemia (CLL) is the most common human (as a negative control) fused with GST in mammalian cells. HEK leukemia. Deregulation of the T-cell leukemia/lymphoma 1 oncogene 293 cells were transfected with Omni-GST-Tcl1 or Omni-GST- (TCL1) in mouse B cells causes a CD5+ leukemia similar to aggressive Dleu7 (as a negative control), followed by GST pulldown. The human CLL. To examine the mechanisms by which Tcl1 protein exerts resulting protein complexes were analyzed by mass spectrometry. its oncogenic activity in B cells, we performed proteomics experiments Table S1 lists the top eight hits found in Tcl1 protein complexes to identify its interacting partners. We found that Tcl1 physically inter- but not in Dleu7 complexes. Interestingly, Pnpt1, a previously acts with de novo DNA methylthansferases Dnmt3A and Dnmt3B. We reported Tcl1 interact