| http://purl.uniprot.org/citations/21552325 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21552325 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21552325 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of I-κB kinases (IKKs) and NF-κB by the human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, is thought to promote cell proliferation and transformation. Paradoxically, expression of Tax in most cells leads to drastic up-regulation of cyclin-dependent kinase inhibitors, p21(CIP1/WAF1) and p27(KIP1), which cause p53-/pRb-independent cellular senescence. Here we demonstrate that p21(CIP1/WAF1)-/p27(KIP1)-mediated senescence constitutes a checkpoint against IKK/NF-κB hyper-activation. Senescence induced by Tax in HeLa cells is attenuated by mutations in Tax that reduce IKK/NF-κB activation and prevented by blocking NF-κB using a degradation-resistant mutant of I-κBα despite constitutive IKK activation. Small hairpin RNA-mediated knockdown indicates that RelA induces this senescence program by acting upstream of the anaphase promoting complex and RelB to stabilize p27(KIP1) protein and p21(CIP1/WAF1) mRNA respectively. Finally, we show that down-regulation of NF-κB by the HTLV-1 anti-sense protein, HBZ, delay or prevent the onset of Tax-induced senescence. We propose that the balance between Tax and HBZ expression determines the outcome of HTLV-1 infection. Robust HTLV-1 replication and elevated Tax expression drive IKK/NF-κB hyper-activation and trigger senescence. HBZ, however, modulates Tax-mediated viral replication and NF-κB activation, thus allowing HTLV-1-infected cells to proliferate, persist, and evolve. Finally, inactivation of the senescence checkpoint can facilitate persistent NF-κB activation and leukemogenesis."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.ppat.1002025"xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.ppat.1002025"xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Yang L."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Yang L."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Shih H.M."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Shih H.M."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Giam C.Z."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Giam C.Z."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Ho Y.K."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Ho Y.K."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Kuo Y.L."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Kuo Y.L."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Zhi H."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/author | "Zhi H."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/name | "PLoS Pathog."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/name | "PLoS Pathog."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/pages | "E1002025"xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/pages | "E1002025"xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/title | "NF-kappaB hyper-activation by HTLV-1 tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ."xsd:string |
| http://purl.uniprot.org/citations/21552325 | http://purl.uniprot.org/core/title | "NF-kappaB hyper-activation by HTLV-1 tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ."xsd:string |