title: SUMOylation of sPRDM16 promotes the progression of acute myeloid leukemia.
abstract: BACKGROUND
  In addition to genetic and epigenetic alteration, post-translational modification of proteins plays a critical role in the initiation, progression and maturation of acute myeloid leukemia (AML).
  
  
  METHODS
  The SUMOylation site of sPRDM16 at K568 was mutated to arginine by site-directed mutagenesis. THP-1 acute myeloid leukemia cells were transduced with a lentivirus containing wild type or K568 mutant sPRDM16. Proliferation, self-renewal and differentiation of transduced THP-1 cells were analyzed both in vitro cell culture and in mouse xenografts. Gene expression profiles were analyzed by RNA-seq.
  
  
  RESULTS
  Overexpression of sPRDM16 promoted proliferation, enhanced self-renewal capacity, but inhibited differentiation of THP-1 acute myeloid leukemia cells. We further confirmed that K568 is a bona fide SUMOylation site on sPRDM16. Mutation of the sPRDM16 SUMOylation site at K568 partially abolished the capacity of sPRDM16 to promote proliferation and inhibit differentiation of acute myeloid leukemia cells both in vitro and in mouse xenografts. Furthermore, THP-1 cells overexpressing sPRDM16-K568R mutant exhibited a distinct gene expression profile from wild type sPRDM16 following incubation with PMA.
  
  
  CONCLUSIONS
  Our results suggest that K568 SUMOylation of sPRDM16 plays an important role in the progression of acute myeloid leukemia.
authors.affiliation: Department of Hematology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Street, Chongqing, 400038, People's Republic of China. dongsonne@yeah.net.
authors.forename: Song
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Hematology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Street, Chongqing, 400038, People's Republic of China. chenjpxn@163.com.
authors.forename: Jieping
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D015973:Gene Expression Regulation, Leukemic; D064593:Heterografts; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D058207:Sumoylation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C416371:PRDM16 protein, human; D014157:Transcription Factors