eprintid: 24135
rev_number: 23
userid: 4439
dir: disk0/00/02/41/35
datestamp: 2015-05-12 19:53:58
lastmod: 2021-03-10 06:16:37
status_changed: 2015-05-12 19:53:58
type: article
metadata_visibility: show
contact_email: koide@pitt.edu
item_issues_count: 0
eprint_status: archive
creators_name: Gao, Y
creators_name: Trivedi, S
creators_name: Ferris, RL
creators_name: Koide, K
creators_email: 
creators_email: 
creators_email: rlf1@pitt.edu
creators_email: koide@pitt.edu
creators_id: 
creators_id: 
creators_id: RLF1
creators_id: KOIDE
title: Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells
ispublished: pub
divisions: sch_as_chemistry
full_text_status: public
abstract: 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
date_type: published
publication: Scientific Reports
volume: 4
refereed: TRUE
centers: cen_other_pittcancerinst
id_number: 10.1038/srep06098
other_id: NLM PMC4138523
pmcid: PMC4138523
pmid: 25139387
citation:   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.       
document_url: http://d-scholarship-dev.library.pitt.edu/24135/1/srep06098.pdf
document_url: http://d-scholarship-dev.library.pitt.edu/24135/4/licence.txt