MDM2 promotes cell motility and invasiveness through a RING-finger independent mechanism

R Polanski; HE Warburton; A Ray-Sinha; T Devling; H Pakula; CARLOS RUBBI; N Vlatkovic; MT Boyd

MDM2 promotes cell motility and invasiveness through a RING-finger independent mechanism

R Polanski, HE Warburton, A Ray-Sinha, T Devling, H Pakula, CARLOS RUBBI, N Vlatkovic, MT Boyd

Medical School

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

21 Citations (Scopus)

Abstract

Recent studies connect MDM2 with increased cell motility, invasion and/or metastasis proposing an MDM2-mediated ubiquitylation-dependent mechanism. Interestingly, in renal cell carcinoma (RCC) p53/MDM2 co-expression is associated with reduced survival which is independently linked with metastasis. We therefore investigated whether expression of p53 and/or MDM2 promotes aggressive cell phenotypes. Our data demonstrate that MDM2 promotes increased motility and invasiveness in RCC cells (N.B. similar results are obtained in non-RCC cells). This study shows for the first time both that endogenous MDM2 significantly contributes to cell motility and that this does not depend upon the MDM2 RING-finger, i.e. is independent of ubiquitylation (and NEDDylation). Our data suggest that protein–protein interactions provide a likely mechanistic basis for MDM2-promoted motility which may constitute future therapeutic targets.

Original language	English
Pages (from-to)	4695-4702
Journal	FEBS Letters
Volume	584
Publication status	Published - 27 Oct 2010

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title = "MDM2 promotes cell motility and invasiveness through a RING-finger independent mechanism",

abstract = "Recent studies connect MDM2 with increased cell motility, invasion and/or metastasis proposing an MDM2-mediated ubiquitylation-dependent mechanism. Interestingly, in renal cell carcinoma (RCC) p53/MDM2 co-expression is associated with reduced survival which is independently linked with metastasis. We therefore investigated whether expression of p53 and/or MDM2 promotes aggressive cell phenotypes. Our data demonstrate that MDM2 promotes increased motility and invasiveness in RCC cells (N.B. similar results are obtained in non-RCC cells). This study shows for the first time both that endogenous MDM2 significantly contributes to cell motility and that this does not depend upon the MDM2 RING-finger, i.e. is independent of ubiquitylation (and NEDDylation). Our data suggest that protein–protein interactions provide a likely mechanistic basis for MDM2-promoted motility which may constitute future therapeutic targets.",

author = "R Polanski and HE Warburton and A Ray-Sinha and T Devling and H Pakula and CARLOS RUBBI and N Vlatkovic and MT Boyd",

year = "2010",

month = oct,

day = "27",

language = "English",

volume = "584",

pages = "4695--4702",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - MDM2 promotes cell motility and invasiveness through a RING-finger independent mechanism

AU - Polanski, R

AU - Warburton, HE

AU - Ray-Sinha, A

AU - Devling, T

AU - Pakula, H

AU - RUBBI, CARLOS

AU - Vlatkovic, N

AU - Boyd, MT

PY - 2010/10/27

Y1 - 2010/10/27

N2 - Recent studies connect MDM2 with increased cell motility, invasion and/or metastasis proposing an MDM2-mediated ubiquitylation-dependent mechanism. Interestingly, in renal cell carcinoma (RCC) p53/MDM2 co-expression is associated with reduced survival which is independently linked with metastasis. We therefore investigated whether expression of p53 and/or MDM2 promotes aggressive cell phenotypes. Our data demonstrate that MDM2 promotes increased motility and invasiveness in RCC cells (N.B. similar results are obtained in non-RCC cells). This study shows for the first time both that endogenous MDM2 significantly contributes to cell motility and that this does not depend upon the MDM2 RING-finger, i.e. is independent of ubiquitylation (and NEDDylation). Our data suggest that protein–protein interactions provide a likely mechanistic basis for MDM2-promoted motility which may constitute future therapeutic targets.

AB - Recent studies connect MDM2 with increased cell motility, invasion and/or metastasis proposing an MDM2-mediated ubiquitylation-dependent mechanism. Interestingly, in renal cell carcinoma (RCC) p53/MDM2 co-expression is associated with reduced survival which is independently linked with metastasis. We therefore investigated whether expression of p53 and/or MDM2 promotes aggressive cell phenotypes. Our data demonstrate that MDM2 promotes increased motility and invasiveness in RCC cells (N.B. similar results are obtained in non-RCC cells). This study shows for the first time both that endogenous MDM2 significantly contributes to cell motility and that this does not depend upon the MDM2 RING-finger, i.e. is independent of ubiquitylation (and NEDDylation). Our data suggest that protein–protein interactions provide a likely mechanistic basis for MDM2-promoted motility which may constitute future therapeutic targets.

M3 - Article (journal)

SN - 0014-5793

VL - 584

SP - 4695

EP - 4702

JO - FEBS Letters

JF - FEBS Letters

ER -

MDM2 promotes cell motility and invasiveness through a RING-finger independent mechanism

Abstract

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