P14ARF promotes accumulation of SUMO-1 conjugated (H)Mdm2

TY - JOUR

T1 - P14ARF promotes accumulation of SUMO-1 conjugated (H)Mdm2

AU - Xirodimas, Dimitris P.

AU - Chisholm, June

AU - Desterro, Joana M. S.

AU - Lane, David P.

AU - Hay, Ronald T.

A2 - Celis, Julio

N1 - dc.publisher: Elsevier dc.description.sponsorship: We would like to thank Drs K. Vousden and C. Sherr for providing us with reagents and Ellis Jaffray for purified SAE1/SAE2, Ubc9 and SUMO-1. This work was funded by Cancer Research UK. D.P.L. is a Gibb fellow of Cancer Research UK.

PY - 2002

Y1 - 2002

N2 - p14ARF tumour suppressor stabilises and activates p53 by directly interacting with (H)Mdm2 [(human) murine double minute 2 homologue] and inhibiting its E3 ubiquitin ligase activity. Here we demonstrate that p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1. Mutational analysis demonstrated that the N-terminus of Mdm2 is a target for p14ARF-mediated SUMO conjugation. SUMO modification requires residues 2–14 in p14ARF that interact with (H)Mdm2 and residues 82–101 in exon 2 involved in nucleolar localisation of p14ARF. These data suggest a novel role for p14ARF as a regulator of activity of (H)Mdm2, which could be related to its tumour suppressing activities.

AB - p14ARF tumour suppressor stabilises and activates p53 by directly interacting with (H)Mdm2 [(human) murine double minute 2 homologue] and inhibiting its E3 ubiquitin ligase activity. Here we demonstrate that p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1. Mutational analysis demonstrated that the N-terminus of Mdm2 is a target for p14ARF-mediated SUMO conjugation. SUMO modification requires residues 2–14 in p14ARF that interact with (H)Mdm2 and residues 82–101 in exon 2 involved in nucleolar localisation of p14ARF. These data suggest a novel role for p14ARF as a regulator of activity of (H)Mdm2, which could be related to its tumour suppressing activities.

KW - Mdm2

KW - Hdm2

U2 - 10.1016/S0014-5793(02)03310-0

DO - 10.1016/S0014-5793(02)03310-0

M3 - Article

SN - 1873-3468

VL - 528

SP - 207

EP - 211

JO - FEBS Letters

JF - FEBS Letters

IS - 1-3

ER -