The MDM2 RING finger is required for cell cycle-dependent regulation of its protein expression

Ling Gu; Haoqiang Ying; Hongwu Zheng; Stephen A. Murray; Zhi Xiong Jim Xiao

doi:10.1016/S0014-5793(03)00502-7

The MDM2 RING finger is required for cell cycle-dependent regulation of its protein expression

Ling Gu, Haoqiang Ying, Hongwu Zheng, Stephen A. Murray, Zhi Xiong Jim Xiao

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

14 Scopus citations

Abstract

The MDM2 oncoprotein is overexpressed in many human tumors and cancers. MDM2 functions as an E3 ligase for p53 and for itself. MDM2 also interacts with the retinoblastoma protein (RB) and the transcription factor E2F1 to promote cell cycle S-phase entry. Here, we report that MDM2 protein expression is cell cycle-regulated, which is dependent on its RING finger domain and requires Lys446. We show that MDM2 protein is stabilized at S phase. In addition, overexpression of MDM2 results in stimulation of E2F activity and accumulation of cells in S phase. These data suggest that ubiquitination of MDM2 is cell cycle-regulated and that MDM2 may play a role in cell cycle progression.

Original language	English (US)
Pages (from-to)	218-222
Number of pages	5
Journal	FEBS Letters
Volume	544
Issue number	1-3
DOIs	https://doi.org/10.1016/S0014-5793(03)00502-7
State	Published - Jun 5 2003
Externally published	Yes

Keywords

Cell cycle
E2F
E3 ligase
MDM2
Protein expression
RING finger

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/S0014-5793(03)00502-7

Cite this

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title = "The MDM2 RING finger is required for cell cycle-dependent regulation of its protein expression",

abstract = "The MDM2 oncoprotein is overexpressed in many human tumors and cancers. MDM2 functions as an E3 ligase for p53 and for itself. MDM2 also interacts with the retinoblastoma protein (RB) and the transcription factor E2F1 to promote cell cycle S-phase entry. Here, we report that MDM2 protein expression is cell cycle-regulated, which is dependent on its RING finger domain and requires Lys446. We show that MDM2 protein is stabilized at S phase. In addition, overexpression of MDM2 results in stimulation of E2F activity and accumulation of cells in S phase. These data suggest that ubiquitination of MDM2 is cell cycle-regulated and that MDM2 may play a role in cell cycle progression.",

keywords = "Cell cycle, E2F, E3 ligase, MDM2, Protein expression, RING finger",

author = "Ling Gu and Haoqiang Ying and Hongwu Zheng and Murray, {Stephen A.} and Xiao, {Zhi Xiong Jim}",

note = "Funding Information: We thank Dr. Jiandong Chen for MDM2 antibodies. This work is supported by NIH Grant R01CA79804 to Z.-X.X. and DOD Grant DAMA17-97-1-7311 to Z.-X.X.",

year = "2003",

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doi = "10.1016/S0014-5793(03)00502-7",

language = "English (US)",

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pages = "218--222",

journal = "FEBS Letters",

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T1 - The MDM2 RING finger is required for cell cycle-dependent regulation of its protein expression

AU - Gu, Ling

AU - Ying, Haoqiang

AU - Zheng, Hongwu

AU - Murray, Stephen A.

AU - Xiao, Zhi Xiong Jim

N1 - Funding Information: We thank Dr. Jiandong Chen for MDM2 antibodies. This work is supported by NIH Grant R01CA79804 to Z.-X.X. and DOD Grant DAMA17-97-1-7311 to Z.-X.X.

PY - 2003/6/5

Y1 - 2003/6/5

N2 - The MDM2 oncoprotein is overexpressed in many human tumors and cancers. MDM2 functions as an E3 ligase for p53 and for itself. MDM2 also interacts with the retinoblastoma protein (RB) and the transcription factor E2F1 to promote cell cycle S-phase entry. Here, we report that MDM2 protein expression is cell cycle-regulated, which is dependent on its RING finger domain and requires Lys446. We show that MDM2 protein is stabilized at S phase. In addition, overexpression of MDM2 results in stimulation of E2F activity and accumulation of cells in S phase. These data suggest that ubiquitination of MDM2 is cell cycle-regulated and that MDM2 may play a role in cell cycle progression.

AB - The MDM2 oncoprotein is overexpressed in many human tumors and cancers. MDM2 functions as an E3 ligase for p53 and for itself. MDM2 also interacts with the retinoblastoma protein (RB) and the transcription factor E2F1 to promote cell cycle S-phase entry. Here, we report that MDM2 protein expression is cell cycle-regulated, which is dependent on its RING finger domain and requires Lys446. We show that MDM2 protein is stabilized at S phase. In addition, overexpression of MDM2 results in stimulation of E2F activity and accumulation of cells in S phase. These data suggest that ubiquitination of MDM2 is cell cycle-regulated and that MDM2 may play a role in cell cycle progression.

KW - Cell cycle

KW - E2F

KW - E3 ligase

KW - MDM2

KW - Protein expression

KW - RING finger

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DO - 10.1016/S0014-5793(03)00502-7

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AN - SCOPUS:0038018467

SN - 0014-5793

VL - 544

SP - 218

EP - 222

JO - FEBS Letters

JF - FEBS Letters

IS - 1-3

ER -

The MDM2 RING finger is required for cell cycle-dependent regulation of its protein expression

Abstract

Keywords

ASJC Scopus subject areas

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