IndraLab

"Thus, we postulated that hypoxia would lead to an enhanced protein protein interaction between E6 and CYLD, thereby allowing for more efficient E6 mediated ubiquitination."

"Hypoxia-induced degradation of CYLD is associated with E6-mediated CYLD ubiquitination."

"Thus, we postulated that hypoxia would lead to an enhanced protein-protein interaction between E6 and CYLD, thereby allowing for more efficient E6-mediated ubiquitination."

"To further define the relationship between E6 and CYLD, we tested whether E6 expression is associated with CYLD polyubiquitination."

"We performed co-immunoprecipitation studies in HeLa and SiHa cells to compare the intensity of the putative E6-CYLD protein-protein interaction in normoxia versus hypoxia."

"It is also plausible that post-translational hydroxylation may take place on a protein involved in formation of a protein complex that includes E6 and CYLD, whereby hydroxylation impairs complex formation and, by extension, the ability of E6 to target CYLD for ubiquitination."

"Indeed, these immunoprecipitation studies demonstrated that E6 and CYLD weakly interact in SiHa and HeLa cells under normoxia ( xref , lanes 2 and 6)."

"It should be noted that E6-mediated degradation of CYLD was specific to cells exposed to prolonged hypoxia, where the physical interaction of E6 and CYLD might be stabilized through posttranslational modifications ( xref )."

"Whether E6 's from low-risk HPV types interact with either CYLD or NFX1-91 is currently unknown."

"E6 interacts with Cylindromatosis (CYLD) deubiquitinase to inactivate the tumor suppressor CYLD and to activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in hypoxic conditions. xref E6 interacts with p300/cAMP response element binding protein (CREB) xref , xref and interferon regulatory factor 3 (IRF-3) xref to regulate gene expression and with c-Myc to induce upregulation of human telomerase reverse transcriptase to promote cell immortalization. xref , xref , xref HPV16 E6 in the cytoplasm is also important for the oncogenic activity through its regulation of signal transduction by interactions with cytoplasmic E6BP (Erc55), xref E6TP1, xref , xref tumor-necrosis factor (TNF) receptor 1 xref and protein tyrosine phosphatase H1. xref In addition to its oncogenic activities, HPV16 E6 also protects HPV16-infected keratinocytes from the innate immune system by suppressing pro-IL-1β expression. xref "

"Thus, the details of hypoxia mediated post-translational regulation of the E6-CYLD interaction remain to elucidated, and may involve a previously unidentified oxygen-sensing hydroxylase."

"Hydroxylase inhibition also resulted in heightened CYLD ubiquitination and enhanced the protein-protein interaction between E6 and CYLD ( xref , compare lanes 2 to 3 and lanes 6 to 7; xref , compare lanes 2 to 3 and lanes 6 to 7; xref )."

"These latter effects are consistent with the results of the protein-protein interactions studies, which demonstrated that E6 does in fact bind to CYLD under normoxic conditions, albeit to a lesser degree than under hypoxia."

"Hydroxylase inhibition also resulted in heightened CYLD ubiquitination and enhanced the protein protein interaction between E6 and CYLD (XREF_FIG, compare lanes 2 to 3 and lanes 6 to 7; XREF_FIG, compare lanes 2 to 3 and lanes 6 to 7; XREF_FIG)."

"Hypoxia leads to enhanced E6-CYLD protein-protein interactions."