p14 Arf promotes small ubiquitin-like modifier conjugation of Werners helicase.
Here we demonstrate a novel p53-independent interaction between the nucleolar tumor suppressors, p14 Arf and Werners helicase (WRN). Binding of p14 Arf to WRN is multivalent and resembles the binding of p14 Arf to Mdm2. Residues 2-14 and 82-101 of p14 Arf and residues in the central region and C terminus of WRN have particular importance for binding. p14 Arf promotes small ubiquitin-like modifier (SUMO) modification of WRN in a synergistic manner with the SUMO-conjugating enzyme, UBCH9. p14 Arf 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-localization. We establish that the ability to promote SUMO conjugation is a general property of the p14 Arf tumor suppressor.
Woods
Yvonne L
YL
CR-UK Cell Transformation Research Group, Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Ninewells Avenue, Dundee DD1 9SY, UK. y.l.woods@dundee.ac.uk
Xirodimas
Dimitris P
DP
Prescott
Alan R
AR
Sparks
Alison
A
Lane
David P
DP
Saville
Mark K
MK
D004265:DNA Helicases / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D025941:Protein Interaction Mapping; D053484:RecQ Helicases; D025842:SUMO-1 Protein / Q000378:metabolism; D017384:Sequence Deletion; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism*; D000071657:Werner Syndrome Helicase
D010446:Peptide Fragments; D025842:SUMO-1 Protein; D025803:Tumor Suppressor Protein p14ARF; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase