p73-Dependent Apoptosis through Death Receptor: Impairment by Human Cytomegalovirus Infection
| Autor: | Hedi Haddada, Daniel Caput, Christian Davrinche, Jérôme Terrasson, Jacqueline Lulé, Sophie Allart, Hélène Martin |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Human cytomegalovirus
Cancer Research Programmed cell death Fas-Associated Death Domain Protein Cell CASP8 and FADD-Like Apoptosis Regulating Protein Apoptosis Biology medicine.disease_cause Receptors Tumor Necrosis Factor Cell Line Tumor medicine Humans Genes Tumor Suppressor fas Receptor skin and connective tissue diseases Receptor neoplasms Adaptor Proteins Signal Transducing Neurons Cisplatin Caspase 8 Tumor Suppressor Proteins Neurogenesis Intracellular Signaling Peptides and Proteins Nuclear Proteins Tumor Protein p73 medicine.disease DNA-Binding Proteins Enzyme Activation medicine.anatomical_structure Oncology Caspases Cytomegalovirus Infections Cancer research Carcinogenesis medicine.drug |
| Zdroj: | Cancer Research. 65:2787-2794 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | The discovery of p73, a p53-related protein with various isotypes resulting from different promoter usage or splicing events, provided new insights into regulation of neurogenesis and tumorigenesis. Among p73 isoforms described thus far, TA-truncated molecules (ΔN) appeared as key proteins according to their antagonistic activity against transcription factor activity of p53 family members. We previously showed that infection by human cytomegalovirus (HCMV) induced drug resistance and altered p53- and p73-dependent apoptosis of infected cells through accumulation of ΔN-p73α. In accordance with the ability of p53 to induce apoptosis through death receptors, we asked whether p73 activation could compensate for p53 deficiency. We showed that p73 transcriptional activity sensitized cells to apoptosis through death receptors in a caspase-dependent pathway. Expression of the death-inducing signaling complex (DISC) proteins was unchanged, whereas p73 activation through either cisplatin treatment or ectopic overexpression induced up-regulation of Fas transcription and expression at cell surface. According to its ability to flood cells with ΔN-p73α, HCMV inhibited p73-dependent Fas-mediated apoptosis, gaining an additional trick to favor its survival in the host cell. Owing to the involvement of p53- and p73-dependent death receptor signaling in development of the central nervous system, immune surveillance of neural cells, and sensitivity of tumors to drugs, our previous and present data prompt us to consider stabilization of ΔN-p73α by HCMV as a possible mechanism in impairment of embryogenesis and in tumorigenesis. |
| Databáze: | OpenAIRE |
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