Pellino 1 promotes lymphomagenesis by deregulating BCL6 polyubiquitination
- Title
- Pellino 1 promotes lymphomagenesis by deregulating BCL6 polyubiquitination
- Author
- 정희용
- Keywords
- TOLL-LIKE RECEPTORS
- Issue Date
- 2014-11
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC, 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
- Citation
- JOURNAL OF CLINICAL INVESTIGATION, 권: 124, 호: 11, 페이지: 4976-4988
- Abstract
- The signai-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 PEW 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.
- URI
- https://www.jci.org/articles/view/75667http://hdl.handle.net/20.500.11754/51271
- ISSN
- 0021-9738; 1558-8238
- DOI
- 10.1172/JCI75667
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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