Journal article
A 19S proteasomal subunit cooperates with an ERK MAPK-regulated degron to regulate accumulation of Fra-1 in tumour cells
JL Pakay, J Diesch, O Gilan, YY Yip, E Sayan, W Kolch, JM Mariadason, RD Hannan, E Tulchinsky, AS Dhillon
Oncogene | NATURE PUBLISHING GROUP | Published : 2012
DOI: 10.1038/onc.2011.375
Abstract
Fos-related antigen-1 (Fra-1) is a member of the Activator Protein-1 (AP-1) transcription factor superfamily that is overexpressed in a variety of cancers, including colon, breast, lung, bladder and brain. High Fra-1 levels are associated with enhanced cell proliferation, survival, migration and invasion. Despite its frequent overexpression, the molecular mechanisms that regulate the accumulation of Fra-1 proteins in tumour cells are not well understood. Here, we show that turnover of Fra-1, which does not require ubiquitylation, is cooperatively regulated by two distinct mechanisms - association with the 19S proteasomal subunit, TBP-1, and by a C-terminal degron, which acts independently of..
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Funding Acknowledgements
We thank Drs Nishida, Satoh, Greer and Gillespie for generously providing reagents used in this study, and Dr Willie Bienvenut for assistance with the mass spectrometry experiments. This work was supported by grants from the National Health and Medical Research Council of Australia (to ASD and RDH) and the Association for International Cancer Research (to ET).