A5102896231- Ubiquitin and proteasome pathways
- T-cell and Retrovirus Studies
- Vector-Borne Animal Diseases
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
Icahn School of Medicine at Mount Sinai
2020-2021
Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T cells associated with chronic infection by human lymphotropic virus type-1 (HTLV-1). ATLL patients aggressive subtypes have dismal outcomes. We demonstrate that co-opt an early checkpoint within the tumor necrosis factor receptor 1 (TNFR1) pathway, resulting in survival advantage. This revolves around interaction between deubiquitinase CYLD and its target RIPK1. The status RIPK1 K63-ubiquitination determines cell fate creating...
TNF ligation of receptor 1 (TNFR1) promotes either inflammation and cell survival by (a) inhibiting RIPK1's death-signaling function activating NF-κB or (b) causing RIPK1 to associate with the death-inducing signaling complex initiate apoptosis necroptosis. The cellular source that results in RIPK1-dependent death remains unclear. To address this, we employed vitro systems murine models T cell–dependent transplant tumor rejection which target susceptibility could be genetically altered. We...