In primary effusion lymphoma cells, MYB transcriptional repression is associated with v-FLIP expression during latent KSHV infection while both v-FLIP and v-GPCR become involved during the lytic cycle

Autor:	Françoise Valensi, Antoine Gessain, Christophe Nicot, Hittu Matta, Renaud Mahieux, Preet M. Chaudhary, Vincent Lacoste, Jean Gabarre
Přispěvatelé:	Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology, Molecular genetics and Immunology, University of Kansas Medical Center [Lawrence], Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Division of Hematology-Oncology and the Hillman Cancer Center, University of Pittsburgh Medical Center, This work was supported by a grant from l'Association de Recherche sur le Cancer (ARC) and from la Fondation de France to RM and grants from NIH (CA85177 and CA124621) to PMC. VL and CN were supported by a bourse Pasteur‐Weissman and la Ligue Nationale Contre le Cancer respectively. RM was supported by a bourse Roux, from the Institut Pasteur and by INSERM., We thank Dr D. Gonzalez‐Dunia, J.S. Seeler and C. Royer‐Leveau for their help. We are indebted to Drs P. Charneau, J. Golay, N. Rice, L. Boxer, P. Murphy and W.C. Greene for generous gifts of reagents essential to the realization of this study. We thank Pr O. Hermine for providing us with some PEL fresh samples, and Dr Timothy Stinear for his critical comments., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Kansas Medical Center [Kansas City, KS, USA], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), University of Kansas Medical Center, Laboratoire d'hématologie ( ERL 8254 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]
Rok vydání:	2007
Předmět:	non-Hodgkinlymphoma Transcription Genetic Genes myb [SDV]Life Sciences [q-bio] viruses CASP8 and FADD-Like Apoptosis Regulating Protein Gene Expression MESH : Sarcoma Kaposi MESH : Herpesvirus 8 Human MESH: Virus Activation Receptors G-Protein-Coupled Transduction (genetics) molecular studies 0302 clinical medicine MESH: Lymphoma Non-Hodgkin/virology Transduction Genetic MESH: Viral Proteins/metabolism Virus latency MESH : Virus Latency MYB MESH : Cell Transformation Viral Viral G-Protein Coupled Receptor MESH : Viral Proteins MESH: Lymphoma AIDS-Related/metabolism Lymphoma AIDS-Related Regulation of gene expression MESH : Trans-Activators 0303 health sciences Lymphoma Non-Hodgkin MESH: Virus Latency NF-kappa B Hematology Transfection MESH : Immediate-Early Proteins MESH: Transduction Genetic MESH: Gene Expression Regulation Viral MESH: Sarcoma Kaposi/metabolism MESH: Herpesvirus 8 Human/physiology Virus Latency 3. Good health Lytic cycle MESH: Cell Transformation Viral MESH : NF-kappa B MESH : Genes myb 030220 oncology & carcinogenesis Herpesvirus 8 Human MESH : Virus Activation MESH : Receptors G-Protein-Coupled Primary effusion lymphoma MESH : Transfection MESH: NF-kappa B/metabolism Gene Expression Regulation Viral MESH: Cell Line Tumor MESH: Gene Expression animal structures MESH : Transduction Genetic MESH : Lymphoma AIDS-Related Biology MESH : Gene Expression Regulation Viral Immediate-Early Proteins Proto-Oncogene Proteins c-myb Viral Proteins 03 medical and health sciences MESH: Receptors G-Protein-Coupled/metabolism MESH: Sarcoma Kaposi/virology MESH: Trans-Activators/metabolism Cell Line Tumor medicine nuclear factor-jB Humans MESH : Lymphoma Non-Hodgkin MESH: CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism Sarcoma Kaposi 030304 developmental biology B cells MESH: Humans MESH : Cell Line Tumor herpes virus MESH: Lymphoma AIDS-Related/virology MESH: Transcription Genetic MESH: Transfection MESH: Immediate-Early Proteins/metabolism MESH : Humans MESH: Proto-Oncogene Proteins c-myb/analysis MESH : Transcription Genetic Kaposi sarcoma MESH : CASP8 and FADD-Like Apoptosis Regulating Protein Cell Transformation Viral medicine.disease MESH : Proto-Oncogene Proteins c-myb MESH : Gene Expression MESH: Genes myb Trans-Activators Cancer research MESH: Lymphoma Non-Hodgkin/metabolism Virus Activation
Zdroj:	British Journal of Haematology British Journal of Haematology, Wiley, 2007, 138 (4), pp.487-501. ⟨10.1111/j.1365-2141.2007.06697.x⟩ British Journal of Haematology, 2007, 138 (4), pp.487-501. ⟨10.1111/j.1365-2141.2007.06697.x⟩ British Journal of Haematology, Wiley, 2007, 138 (4), pp.487-501. 〈10.1111/j.1365-2141.2007.06697.x〉
ISSN:	1365-2141 0007-1048
Popis:	International audience; Primary effusion lymphoma (PEL) is a rare, distinct subtype of non-Hodgkin lymphoma, which is associated with Kaposi sarcoma-associated herpesvirus (KSHV) infection. Although MYB levels are high in most neoplastic B cells, we found that, unexpectedly, both PEL cells and uncultured PEL patients' samples contained very low levels of MYB mRNA when compared to B-cell leukaemia samples obtained from KSHV(-) patients. These results were further confirmed at the protein level. Both latent viral FLICE inhibitory protein (v-FLIP) and early lytic viral G protein coupled receptor (v-GPCR) KSHV proteins were found to activate nuclear factor (NF)-kappaB and transrepress a MYB promoter reporter construct. In contrast, a dominant negative inhibitor of NF-kappaB (IkappaB-alpha) mutant prevented v-FLIP and v-GPCR from inhibiting MYB functions while a v-GPCR mutant that was impaired for NF-kappaB activation could not repress the MYB construct. Transduction of a v-FLIP expressing vector or stable transfection of v-GPCR both resulted in a marked downregulation of the endogenous MYB protein expression. However, MYB expression transactivated the lytic switch Replication and Transcription Activator (RTA) promoter in transient transfection assays. Taken together, our results demonstrate that, contrary to a number of other haematological malignancies, MYB expression is not required for PEL cell proliferation. Repressing MYB expression also helps in maintaining the virus in latency.
Databáze:	OpenAIRE
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