Journal article
Transketolase regulates sensitivity to APR-246 in p53-null cells independently of oxidative stress modulation
JV Milne, BZ Zhang, KM Fujihara, S Dawar, WA Phillips, NJ Clemons
Scientific Reports | NATURE PORTFOLIO | Published : 2021
Abstract
The prevalence and dire implications of mutations in the tumour suppressor, p53, highlight its appeal as a chemotherapeutic target. We recently showed that impairing cellular antioxidant systems via inhibition of SLC7A11, a component of the system xc− cystine-glutamate antiporter, enhances sensitivity to mutant-p53 targeted therapy, APR-246. We investigated whether this synergy extends to other genes, such as those encoding enzymes of the pentose phosphate pathway (PPP). TKT, one of the major enzymes of the PPP, is allegedly regulated by NRF2, which is in turn impaired by accumulated mutant-p53 protein. Therefore, we investigated the relationship between mutant-p53, TKT and sensitivity to AP..
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Awarded by Australian Cancer Research Foundation
Funding Acknowledgements
We thank the following Peter MacCallum Cancer Centre core facilities: Flow Cytometry, Victorian Centre for Functional Genomics. This research was supported by a National Health and Medical Research Council (NHMRC) Project Grant #APP1120293 (W.A.P. and N.J.C.) and the Australian Cancer Research Foundation (for the Peter MacCallum Cancer Centre Flow Cytometry facility and Victorian Centre for Functional Genomics). J.V.M. and K.M.F. are supported by an Australian Government Research Training Program (RTP) Scholarship. N.J.C. is supported by a Fellowship (MCRF16002) from the Department of Health and Human Services acting through the Victorian Cancer Agency, Victoria, Australia.