RELT stains prominently in B-cell lymphomas and binds the hematopoietic transcription factor MDFIC

Biochemistry and Biophysics Reports

Yasmeen Alhomsy¹  John K. Cusick²  Stephanie Wong²  Nazila Hejazi³  Aaron T. Jacobs⁴  Yihui Shi⁵  George Talbott⁵  Cara Hart⁶  Vladimir N. Uversky⁷ 

[1] Corresponding author. California Northstate University College of Medicine, Elk Grove, CA, USA.;Department of Basic Science, California Northstate University, College of Medicine, Elk Grove, CA, 95757, USA;Department of Biology, The University of Hawaii at Hilo, Hilo, HI, 96720, USA;Department of Clinical Science, California Northstate University, College of Medicine, Elk Grove, CA, 95757, USA;Department of Medical Education, California University of Science and Medicine, San Bernardino, CA, 92408, USA;Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA;Department of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA, 95757, USA;

关键词: RELT;    RELL1;    RELL2;    TNFRSF;    MDFIC;    B-Cell lymphoma;   

DOI  :  

来源: DOAJ

【 摘 要 】

Receptor Expressed in Lymphoid Tissues (RELT) is a human tumor necrosis factor receptor superfamily member (TNFRSF) that is expressed most prominently in cells and tissues of the hematopoietic system. RELL1 and RELL2 are two homologs that physically interact with RELT and co-localize with RELT at the plasma membrane. This study sought to further elucidate the function of RELT by identifying novel protein interactions with RELT family members. The transcription factor MyoD family inhibitor domain-containing (MDFIC) was identified in a yeast two-hybrid genetic screen using RELL1 as bait. MDFIC co-localizes with RELT family members at the plasma membrane; this co-localization was most prominently observed with RELL1 and RELL2. In vitro co-immunoprecipitation (Co-IP) was utilized to demonstrate that MDFIC physically interacts with RELT, RELL1, and RELL2. Co-IP using deletion mutants of MDFIC and RELT identified regions important for physical association between MDFIC and RELT family members and a computational analysis revealed that RELT family members are highly disordered proteins. Immunohistochemistry of normal human lymph nodes revealed RELT staining that was most prominent in macrophages. Interestingly, the level of RELT staining significantly increased progressively in low and high-grade B-cell lymphomas versus normal lymph nodes. RELT co-staining with CD20 was observed in B-cell lymphomas, indicating that RELT is expressed in malignant B cells. Collectively, these results further our understanding of RELT-associated signaling pathways, the protein structure of RELT family members, and provide preliminary evidence indicating an association of RELT with B-cell lymphomas.

【 授权许可】

Unknown