relation: http://d-scholarship-dev.library.pitt.edu/24135/
title: Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells
creator: Gao, Y
creator: Trivedi, S
creator: Ferris, RL
creator: Koide, K
description: ABT-737 inhibits the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and BCL-X L. Meayamycin B switches the splicing pattern of myeloid cell leukemia factor 1 (MCL1) pre-mRNA. Specifically, inhibition of splicing factor 3B subunit 1 (SF3B1) with meayamycin B promotes the generation of the proapoptotic, short splicing variant (MCL1-S) and diminishes the antiapoptotic, long variant (MCL1-L). This action was previously associated with the cytotoxicity of meayamycin B in non-small cell lung carcinoma cell lines. ABT-737 induced apoptosis in response to an ablation of MCL1-L by meayamycin B. In this study, we further exploited this synergistic combination in head and neck squamous cell carcinoma (HNSCC), up to 90% of which overexpress MCL1 and BCL-X L. In a panel of seven HNSCC cell lines, the combination of meayamycin B and ABT-737 rapidly triggered a Bax/Bak-mediated apoptosis that overcame the resistance from HPV16-positive HNSCC against each agent alone. Both RT-PCR and Western blotting showed that meayamycin B up-regulated MCL1-S and down-regulated MCL1-L. Significantly, we discovered that SF3B1 was involved in the splicing of oncogenic HPV16 E6 to produce non-oncogenic HPV16 E6*, indicating that SF3B1 may inhibit HPV16-induced tumorigenesis.
date: 2014-08-20
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24135/1/srep06098.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/24135/4/licence.txt
identifier:   Gao, Y and Trivedi, S and Ferris, RL and Koide, K  (2014) Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells.  Scientific Reports, 4.       
relation: 10.1038/srep06098