title: Silencing autocrine death: a ubiquitin ligase that blocks activation-induced cell death in cutaneous T-cell lymphoma.
abstract: Cutaneous T-cell lymphoma (CTCL) tumor cells lack the ability of activated T cells to undergo TCR/CD3-mediated activation-induced cell death (AICD). In this issue, the study reported by Wu et al. demonstrates that c-CBL (Casitas B-lineage Lymphoma proto-oncogene) is overexpressed in CTCL. When CTCL cells lose c-CBL, AICD is enhanced. Furthermore, combination therapy with methotrexate (a known demethylating agent for the CD95 gene) in combination with the loss of c-CBL increases CTCL cell death. Therefore, inhibition of c-CBL could represent a method of sensitizing lymphoma cells to enhance AICD. Armed with their novel data, the investigators envision combination therapies that target c-CBL to reactivate AICD in the malignant T cells whenever responsiveness to TCR/CD3 signaling is retained.
authors: Departments of Dermatology, Venereology, and Allergology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.
authors: Claus-Detlev
authors: CD
authors: Klemke
authors: Section of Molecular Dermatology, Departments of Dermatology, Venereology, and Allergology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.
authors: Maria
authors: M
authors: Feoktistova
authors: Departments of Dermatology, Venereology, and Allergology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany; Section of Molecular Dermatology, Departments of Dermatology, Venereology, and Allergology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany. Electronic address: Martin.Leverkus@medma.uni-heidelberg.de.
authors: Martin
authors: M
authors: Leverkus
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism*; D008297:Male; D000090063:Proto-Oncogene Mas; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering; D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human