title: Pellino 1 promotes lymphomagenesis by deregulating BCL6 polyubiquitination.
abstract: The signal-responsive E3 ubiquitin ligase pellino 1 (PELI1) regulates TLR and T cell receptor (TCR) signaling and contributes to the maintenance of autoimmunity; however, little is known about the consequence of mutations that result in upregulation of PELI1. Here, we developed transgenic mice that constitutively express human PELI1 and determined that these mice have a shorter lifespan due to tumor formation. Constitutive expression of PELI1 resulted in ligand-independent hyperactivation of B cells and facilitated the development of a wide range of lymphoid tumors, with prominent B cell infiltration observed across multiple organs. PELI1 directly interacted with the oncoprotein B cell chronic lymphocytic leukemia (BCL6) and induced lysine 63-mediated BCL6 polyubiquitination. In samples from patients with diffuse large B cell lymphomas (DLBCLs), PELI1 expression levels positively correlated with BCL6 expression, and PELI1 overexpression was closely associated with poor prognosis in DLBCLs. Together, these results suggest that increased PELI1 expression and subsequent induction of BCL6 promotes lymphomagenesis and that this pathway may be a potential target for therapeutic strategies to treat B cell lymphomas.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Heounjeong
authors.initials: H
authors.lastname: Go
authors.forename: Ha Rim
authors.initials: HR
authors.lastname: Song
authors.forename: Suhyeon
authors.initials: S
authors.lastname: Kim
authors.forename: Geun-Hyoung
authors.initials: GH
authors.lastname: Ha
authors.forename: Yoon-Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.forename: Hyeseong
authors.initials: H
authors.lastname: Cho
authors.forename: Ho Chul
authors.initials: HC
authors.lastname: Kang
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Chul-Woo
authors.initials: CW
authors.lastname: Kim
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Lee
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D042583:Lymphangiogenesis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000401:mortality; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000502:physiology*; D025821:Polyubiquitin / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D055550:Protein Stability; D051560:Proto-Oncogene Proteins c-bcl-6; D012372:ROC Curve; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D054875:Ubiquitination
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D025821:Polyubiquitin; C485959:PELI1 protein, human; D044767:Ubiquitin-Protein Ligases