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P14ARF promotes accumulation of SUMO‐1 conjugated (H)Mdm2
Author(s) -
Xirodimas Dimitris P,
Chisholm June,
Desterro Joana M.S,
Lane David P,
Hay Ronald T
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03310-0
Subject(s) - conjugated system , chemistry , mdm2 , p14arf , cancer research , microbiology and biotechnology , biochemistry , biology , organic chemistry , apoptosis , carcinogenesis , gene , tumor suppressor gene , polymer
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.