RELT stains prominently in B-cell lymphomas and binds the hematopoietic transcription factor MDFIC
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 th...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Biochemistry and Biophysics Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580820301783 |
| _version_ | 1818644020939718656 |
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| author | John K. Cusick Yasmeen Alhomsy Stephanie Wong George Talbott Vladimir N. Uversky Cara Hart Nazila Hejazi Aaron T. Jacobs Yihui Shi |
| author_facet | John K. Cusick Yasmeen Alhomsy Stephanie Wong George Talbott Vladimir N. Uversky Cara Hart Nazila Hejazi Aaron T. Jacobs Yihui Shi |
| author_sort | John K. Cusick |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T00:08:13Z |
| format | Article |
| id | doaj.art-c9644ff27a5a4238a9fe07291b266c1d |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-17T00:08:13Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-c9644ff27a5a4238a9fe07291b266c1d2022-12-21T22:10:53ZengElsevierBiochemistry and Biophysics Reports2405-58082020-12-0124100868RELT stains prominently in B-cell lymphomas and binds the hematopoietic transcription factor MDFICJohn K. Cusick0Yasmeen Alhomsy1Stephanie Wong2George Talbott3Vladimir N. Uversky4Cara Hart5Nazila Hejazi6Aaron T. Jacobs7Yihui Shi8Department of Basic Science, California Northstate University, College of Medicine, Elk Grove, CA, 95757, USA; 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, USADepartment of Medical Education, California University of Science and Medicine, San Bernardino, CA, 92408, USADepartment of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA, 95757, USADepartment of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USADepartment of Biology, The University of Hawaii at Hilo, Hilo, HI, 96720, USADepartment of Clinical Science, California Northstate University, College of Medicine, Elk Grove, CA, 95757, USADepartment of Medical Education, California University of Science and Medicine, San Bernardino, CA, 92408, USADepartment of Basic Science, California Northstate University, College of Medicine, Elk Grove, CA, 95757, USAReceptor 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.http://www.sciencedirect.com/science/article/pii/S2405580820301783RELTRELL1RELL2TNFRSFMDFICB-Cell lymphoma |
| spellingShingle | John K. Cusick Yasmeen Alhomsy Stephanie Wong George Talbott Vladimir N. Uversky Cara Hart Nazila Hejazi Aaron T. Jacobs Yihui Shi RELT stains prominently in B-cell lymphomas and binds the hematopoietic transcription factor MDFIC Biochemistry and Biophysics Reports RELT RELL1 RELL2 TNFRSF MDFIC B-Cell lymphoma |
| title | RELT stains prominently in B-cell lymphomas and binds the hematopoietic transcription factor MDFIC |
| title_full | RELT stains prominently in B-cell lymphomas and binds the hematopoietic transcription factor MDFIC |
| title_fullStr | RELT stains prominently in B-cell lymphomas and binds the hematopoietic transcription factor MDFIC |
| title_full_unstemmed | RELT stains prominently in B-cell lymphomas and binds the hematopoietic transcription factor MDFIC |
| title_short | RELT stains prominently in B-cell lymphomas and binds the hematopoietic transcription factor MDFIC |
| title_sort | relt stains prominently in b cell lymphomas and binds the hematopoietic transcription factor mdfic |
| topic | RELT RELL1 RELL2 TNFRSF MDFIC B-Cell lymphoma |
| url | http://www.sciencedirect.com/science/article/pii/S2405580820301783 |
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