Activation of non-canonical NF-kappaB pathway mediated by STP-A11, an oncoprotein of Herpesvirus saimiri.
Although Saimiri Transforming Protein (STP)-A11, an oncoprotein of Herpesvirus saimiri, has been known to activate NF-kappaB signaling pathway, the detailed mechanism has not been reported yet. We herein report that STP-A11 activates non-canonical NF-kappaB pathway, resulting in p100 processing to p52. In addition, translocation of p52 protein (NF-kappaB2) into the nucleus is observed by the expression of STP-A11. STP-A11-mediated processing of p100 to p52 protein requires proteosome-mediated proteolysis because MG132 treatment clearly blocked p52 production in spite of the expression of STP-A11. Analysis of STP-A11 mutants to activate NF-kappaB2 pathway discloses the requirement of TRAF6-binding site not Src-binding site for STP-A11-mediated NF-kappaB2 pathway. Blockage of STP-A11-mediated p52 production using siRNA against p52 enhanced a chemotherapeutic drug-mediated cell death, suggesting that p52 production induced by the expression of STP-A11 would contribute to cellular transformation, which results from a resistance to cell death.
Cho
Il-Rae
IR
Department of Nanomedical Engineering, Joint-Research Center of Pusan National University-Fraunhofer IGB, Pusan National University, Miryang, Gyeongnam 627-706, Korea.
Jeong
Sunam
S
Jhun
Byung Hak
BH
An
Won G
WG
Lee
BokSoo
B
Kwak
Youn-Tae
YT
Lee
Sun-Hwa
SH
Jung
Jae U
JU
Chung
Young-Hwa
YH
D016923:Cell Death; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006567:Herpesvirus 2, Saimiriine / Q000502:physiology*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D052003:NF-kappa B p52 Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D061988:Proteasome Inhibitors; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism
D004791:Enzyme Inhibitors; D007976:Leupeptins; D052003:NF-kappa B p52 Subunit; D009856:Oncogene Proteins, Viral; D061988:Proteasome Inhibitors; D034741:RNA, Small Interfering; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde