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M405414200v1
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Papers In Press, published online ahead of print September 7, 2004
J. Biol. Chem, 10.1074/jbc.M405414200
Submitted on May 14, 2004
Revised on August 17, 2004
Accepted on September 3, 2004

p14Arf promotes SUMO conjugation of Werners helicase

Yvonne L. Woods, Dimitris P. Xirodimas, Alan R. Prescott, Alison Sparks, David P. Lane, and Mark K. Saville

Surgery And Molecular Oncology, University Of Dundee, Ninewells Hospital And Medical School, Dundee, Tayside DD1 9SY

Corresponding Author: y.l.woods{at}dundee.ac.uk

Here we demonstrate a novel p53-independent interaction between the nucleolar tumour suppressors, p14Arf and Werners helicase (WRN). Binding of p14Arf to WRN is multivalent and resembles the binding of p14Arf to Mdm2. Residues 2-14 and 82-101 of p14Arf, and residues in the central region and C-terminus of WRN have particular importance for binding. p14Arf promotes SUMO modification of WRN in a synergistic manner with the SUMO-conjugating enzyme, UBCH9. p14Arf causes redistribution of WRN within the nucleus and this effect is reversed by expression of a SUMO-specific protease, thus implicating the SUMO conjugation pathway in WRN re-localisation. We establish that the ability to promote SUMO conjugation is a general property of the p14Arf tumour suppressor.


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