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

Dimitris P. Xirodimas; June Chisholm; Joana M. S. Desterro; David P. Lane; Ronald T. Hay; Julio Celis

doi:10.1016/S0014-5793(02)03310-0

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

Dimitris P. Xirodimas
, June Chisholm
, Joana M. S. Desterro
, David P. Lane
, Ronald T. Hay
, Julio Celis (Editor)

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	207-211
Number of pages	5
Journal	FEBS Letters
Volume	528
Issue number	1-3
DOIs	https://doi.org/10.1016/S0014-5793(02)03310-0
Publication status	Published - 2002

Keywords

Mdm2
Hdm2

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10.1016/S0014-5793(02)03310-0

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@article{6622a320b7f24b31b6f63c36fcd1e0d6,

title = "P14ARF promotes accumulation of SUMO-1 conjugated (H)Mdm2",

abstract = "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{\textendash}14 in p14ARF that interact with (H)Mdm2 and residues 82{\textendash}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.",

keywords = "Mdm2, Hdm2",

author = "Xirodimas, \{Dimitris P.\} and June Chisholm and Desterro, \{Joana M. S.\} and Lane, \{David P.\} and Hay, \{Ronald T.\} and Julio Celis",

note = "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. ",

year = "2002",

doi = "10.1016/S0014-5793(02)03310-0",

language = "English",

volume = "528",

pages = "207--211",

journal = "FEBS Letters",

issn = "1873-3468",

publisher = "Wiley",

number = "1-3",

}

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 -

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

Abstract

Keywords

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