The endogenous HBZ interactome in ATL leukemic cells reveals an unprecedented complexity of host interacting partners involved in RNA splicing

ABSTRACT: Five percent of HTLV-1 infected subjects develops an untreatable form of cancer designated Adult T cell leukemia (ATL). The HTLV-1-encoded HBZ protein is believed to act as a viral oncogene by disarranging crucial pathways in the infected cells. Key to thisfunction is a progressive cytoplasmic-to-nuclear dislocation of HBZ and its interaction with nuclear factors whose complexity wasnot assessed until now. In this investigation we unveiled for the first time such complexity by studying the endogenous HBZinteractome in a leukemic cell line derived from an ATL patient. A high number of nuclear interactors, represented by at least 249members, were found. Among the various family of interactors, we found predominant the family involved in RNA splicing and RNAstability. A disarrangement of the splicing mechanism was demonstrated both in ATL cells and in non HTLV-1-derived leukemic cellsexpressing HBZ after genetic transfer, strongly suggesting that a major mechanism leading to HTLV-1-mediated transformationand persistence of the oncogenic state is related to this event. Our unprecedented results shed new light on the mechanisms bywhich a human retrovirus can alter the infected cell metabolism and strongly predispose and/or maintain neoplastictransformation

ORGANISM(S): Homo sapiens

PROVIDER: GSE206085 | GEO | 2022/07/27

REPOSITORIES: GEO