MDM2 interacts with and downregulates a sarcomeric protein, TCAP

Li Feng Tian; Hui Yan Li; Bao Feng Jin; Xin Pan; Jiang Hong Man; Pei Jing Zhang; Wei Hua Li; Bing Liang; Hui Liu; Jie Zhao; Wei Li Gong; Tao Zhou; Xue Min Zhang

doi:10.1016/j.bbrc.2006.04.108

MDM2 interacts with and downregulates a sarcomeric protein, TCAP

Li Feng Tian, Hui Yan Li, Bao Feng Jin, Xin Pan, Jiang Hong Man, Pei Jing Zhang, Wei Hua Li, Bing Liang, Hui Liu, Jie Zhao, Wei Li Gong, Tao Zhou, Xue Min Zhang

Experimental Radiation Oncology

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

37 Scopus citations

Abstract

Recent reports have shown that MDM2 may attenuate hypertrophy of cardiac myocytes. However, mechanism of MDM2 involving in this process is unclear. In this study, we identified a novel specific MDM2-binding protein TCAP by the yeast two-hybrid screen. It was validated by GST pull-down and co-immunoprecipitation assays. Confocal analysis showed that MDM2 and TCAP co-localized in the nucleus, and elevated MDM2 expression could alter the subcellular localization of TCAP. Notably, MDM2 downregulated the protein level of TCAP through the proteasomal pathway, and this downregulation was inhibited by p14^ARF. In addition, our results suggested that the degradation of TCAP by MDM2 was through the ubiquitin-independent pathway. Given that TCAP is a key component involving in the cardiac hypertrophy, the degradation of TCAP by MDM2 might be connected with the roles of MDM2 in cardiac hypertrophy. Further investigation will focus on the biological significance of MDM2-TCAP interaction in cardiac hypertrophy.

Original language	English (US)
Pages (from-to)	355-361
Number of pages	7
Journal	Biochemical and biophysical research communications
Volume	345
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2006.04.108
State	Published - Jun 23 2006

Keywords

Cardiac hypertrophy
Degradation
Interaction
MDM2
TCAP
Yeast two-hybrid screen
p14

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2006.04.108

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@article{0024e5ff7fdc473ebba732396bafa235,

title = "MDM2 interacts with and downregulates a sarcomeric protein, TCAP",

abstract = "Recent reports have shown that MDM2 may attenuate hypertrophy of cardiac myocytes. However, mechanism of MDM2 involving in this process is unclear. In this study, we identified a novel specific MDM2-binding protein TCAP by the yeast two-hybrid screen. It was validated by GST pull-down and co-immunoprecipitation assays. Confocal analysis showed that MDM2 and TCAP co-localized in the nucleus, and elevated MDM2 expression could alter the subcellular localization of TCAP. Notably, MDM2 downregulated the protein level of TCAP through the proteasomal pathway, and this downregulation was inhibited by p14ARF. In addition, our results suggested that the degradation of TCAP by MDM2 was through the ubiquitin-independent pathway. Given that TCAP is a key component involving in the cardiac hypertrophy, the degradation of TCAP by MDM2 might be connected with the roles of MDM2 in cardiac hypertrophy. Further investigation will focus on the biological significance of MDM2-TCAP interaction in cardiac hypertrophy.",

keywords = "Cardiac hypertrophy, Degradation, Interaction, MDM2, TCAP, Yeast two-hybrid screen, p14",

author = "Tian, {Li Feng} and Li, {Hui Yan} and Jin, {Bao Feng} and Xin Pan and Man, {Jiang Hong} and Zhang, {Pei Jing} and Li, {Wei Hua} and Bing Liang and Hui Liu and Jie Zhao and Gong, {Wei Li} and Tao Zhou and Zhang, {Xue Min}",

note = "Funding Information: We thank Dr. Scheffner, M. for kindly providing the pcDNA3-HA-MDM2 plasmid and Dr. Peter, G. for pEGFP-p14 ARF plasmid. We are also grateful to Dr. Pei, G. for the mouse pcDNA3-GFP-MDM2 plasmid. This work was supported by 973 National Program of China (2004CB518800), grants from Beijing Scientific and Technology Committee, and grants from National Natural Science foundation of China (and 30270299).",

year = "2006",

month = jun,

day = "23",

doi = "10.1016/j.bbrc.2006.04.108",

language = "English (US)",

volume = "345",

pages = "355--361",

journal = "Biochemical and biophysical research communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "1",

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TY - JOUR

T1 - MDM2 interacts with and downregulates a sarcomeric protein, TCAP

AU - Tian, Li Feng

AU - Li, Hui Yan

AU - Jin, Bao Feng

AU - Pan, Xin

AU - Man, Jiang Hong

AU - Zhang, Pei Jing

AU - Li, Wei Hua

AU - Liang, Bing

AU - Liu, Hui

AU - Zhao, Jie

AU - Gong, Wei Li

AU - Zhou, Tao

AU - Zhang, Xue Min

N1 - Funding Information: We thank Dr. Scheffner, M. for kindly providing the pcDNA3-HA-MDM2 plasmid and Dr. Peter, G. for pEGFP-p14 ARF plasmid. We are also grateful to Dr. Pei, G. for the mouse pcDNA3-GFP-MDM2 plasmid. This work was supported by 973 National Program of China (2004CB518800), grants from Beijing Scientific and Technology Committee, and grants from National Natural Science foundation of China (and 30270299).

PY - 2006/6/23

Y1 - 2006/6/23

N2 - Recent reports have shown that MDM2 may attenuate hypertrophy of cardiac myocytes. However, mechanism of MDM2 involving in this process is unclear. In this study, we identified a novel specific MDM2-binding protein TCAP by the yeast two-hybrid screen. It was validated by GST pull-down and co-immunoprecipitation assays. Confocal analysis showed that MDM2 and TCAP co-localized in the nucleus, and elevated MDM2 expression could alter the subcellular localization of TCAP. Notably, MDM2 downregulated the protein level of TCAP through the proteasomal pathway, and this downregulation was inhibited by p14ARF. In addition, our results suggested that the degradation of TCAP by MDM2 was through the ubiquitin-independent pathway. Given that TCAP is a key component involving in the cardiac hypertrophy, the degradation of TCAP by MDM2 might be connected with the roles of MDM2 in cardiac hypertrophy. Further investigation will focus on the biological significance of MDM2-TCAP interaction in cardiac hypertrophy.

AB - Recent reports have shown that MDM2 may attenuate hypertrophy of cardiac myocytes. However, mechanism of MDM2 involving in this process is unclear. In this study, we identified a novel specific MDM2-binding protein TCAP by the yeast two-hybrid screen. It was validated by GST pull-down and co-immunoprecipitation assays. Confocal analysis showed that MDM2 and TCAP co-localized in the nucleus, and elevated MDM2 expression could alter the subcellular localization of TCAP. Notably, MDM2 downregulated the protein level of TCAP through the proteasomal pathway, and this downregulation was inhibited by p14ARF. In addition, our results suggested that the degradation of TCAP by MDM2 was through the ubiquitin-independent pathway. Given that TCAP is a key component involving in the cardiac hypertrophy, the degradation of TCAP by MDM2 might be connected with the roles of MDM2 in cardiac hypertrophy. Further investigation will focus on the biological significance of MDM2-TCAP interaction in cardiac hypertrophy.

KW - Cardiac hypertrophy

KW - Degradation

KW - Interaction

KW - MDM2

KW - TCAP

KW - Yeast two-hybrid screen

KW - p14

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EP - 361

JO - Biochemical and biophysical research communications

JF - Biochemical and biophysical research communications

IS - 1

ER -

MDM2 interacts with and downregulates a sarcomeric protein, TCAP

Abstract

Keywords

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