MDM2 interacts with MDMX through their RING finger domains

Shyu Tanimura; Satoshi Ohtsuka; Kaoru Mitsui; Kazuo Shirouzu; Akihiko Yoshimura; Motoaki Ohtsubo

doi:10.1016/S0014-5793(99)00254-9

MDM2 interacts with MDMX through their RING finger domains

Shyu Tanimura, Satoshi Ohtsuka, Kaoru Mitsui, Kazuo Shirouzu, Akihiko Yoshimura, Motoaki Ohtsubo

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

267 Citations (Scopus)

Abstract

The N-terminus of MDM2 proto-oncoprotein interacts with p53 and down modulates p53 activity by inhibiting transcriptional activity and promoting p53 degradation. MDMX is structurally related to MDM2 and also binds to p53. However, the function of MDMX has not been clarified yet. We found that MDM2 hetero-oligomerized with MDMX through their C-terminal RING finger domains. Yeast two-hybrid analysis revealed that the hetero-oligomerization between MDMX and MDM2 was more stable than the homo-oligomerization of each protein. MDM2 has been shown to be degraded by the ubiquitin-proteasome pathway, while MDMX was a stable protein. Interaction of MDMX with MDM2 through the C-terminal RING finger domains resulted in inhibiting degradation of MDM2. These data indicate that MDMX functions as a regulator of MDM2. Copyright (C) 1999 Federation of European Biochemical Societies.

Original language	English
Pages (from-to)	5-9
Number of pages	5
Journal	FEBS Letters
Volume	447
Issue number	1
DOIs	https://doi.org/10.1016/S0014-5793(99)00254-9
Publication status	Published - 1999 Mar 19
Externally published	Yes

Keywords

MDM2
MDMX
RING finger
p53

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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Cite this

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title = "MDM2 interacts with MDMX through their RING finger domains",

abstract = "The N-terminus of MDM2 proto-oncoprotein interacts with p53 and down modulates p53 activity by inhibiting transcriptional activity and promoting p53 degradation. MDMX is structurally related to MDM2 and also binds to p53. However, the function of MDMX has not been clarified yet. We found that MDM2 hetero-oligomerized with MDMX through their C-terminal RING finger domains. Yeast two-hybrid analysis revealed that the hetero-oligomerization between MDMX and MDM2 was more stable than the homo-oligomerization of each protein. MDM2 has been shown to be degraded by the ubiquitin-proteasome pathway, while MDMX was a stable protein. Interaction of MDMX with MDM2 through the C-terminal RING finger domains resulted in inhibiting degradation of MDM2. These data indicate that MDMX functions as a regulator of MDM2. Copyright (C) 1999 Federation of European Biochemical Societies.",

keywords = "MDM2, MDMX, RING finger, p53",

author = "Shyu Tanimura and Satoshi Ohtsuka and Kaoru Mitsui and Kazuo Shirouzu and Akihiko Yoshimura and Motoaki Ohtsubo",

note = "Funding Information: We thank Ms. H. Ohgusu and Ms. M. Sasaki for excellent technical assistance and Ms. M. Chikushi for preparing the manuscript. Part of this work was supported by grants from the Ministry of Science, Education and Culture of Japan, the Uehara Memorial Foundation, the TORAY Research Foundation, the Naito Memorial Foundation, the Sumitomo Foundation, the Novartis Foundation and the Kanae Research Foundation. M.O. is supported by a fellowship from the Leukemia Association of America.",

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AU - Tanimura, Shyu

AU - Ohtsuka, Satoshi

AU - Mitsui, Kaoru

AU - Shirouzu, Kazuo

AU - Yoshimura, Akihiko

AU - Ohtsubo, Motoaki

N1 - Funding Information: We thank Ms. H. Ohgusu and Ms. M. Sasaki for excellent technical assistance and Ms. M. Chikushi for preparing the manuscript. Part of this work was supported by grants from the Ministry of Science, Education and Culture of Japan, the Uehara Memorial Foundation, the TORAY Research Foundation, the Naito Memorial Foundation, the Sumitomo Foundation, the Novartis Foundation and the Kanae Research Foundation. M.O. is supported by a fellowship from the Leukemia Association of America.

PY - 1999/3/19

Y1 - 1999/3/19

N2 - The N-terminus of MDM2 proto-oncoprotein interacts with p53 and down modulates p53 activity by inhibiting transcriptional activity and promoting p53 degradation. MDMX is structurally related to MDM2 and also binds to p53. However, the function of MDMX has not been clarified yet. We found that MDM2 hetero-oligomerized with MDMX through their C-terminal RING finger domains. Yeast two-hybrid analysis revealed that the hetero-oligomerization between MDMX and MDM2 was more stable than the homo-oligomerization of each protein. MDM2 has been shown to be degraded by the ubiquitin-proteasome pathway, while MDMX was a stable protein. Interaction of MDMX with MDM2 through the C-terminal RING finger domains resulted in inhibiting degradation of MDM2. These data indicate that MDMX functions as a regulator of MDM2. Copyright (C) 1999 Federation of European Biochemical Societies.

AB - The N-terminus of MDM2 proto-oncoprotein interacts with p53 and down modulates p53 activity by inhibiting transcriptional activity and promoting p53 degradation. MDMX is structurally related to MDM2 and also binds to p53. However, the function of MDMX has not been clarified yet. We found that MDM2 hetero-oligomerized with MDMX through their C-terminal RING finger domains. Yeast two-hybrid analysis revealed that the hetero-oligomerization between MDMX and MDM2 was more stable than the homo-oligomerization of each protein. MDM2 has been shown to be degraded by the ubiquitin-proteasome pathway, while MDMX was a stable protein. Interaction of MDMX with MDM2 through the C-terminal RING finger domains resulted in inhibiting degradation of MDM2. These data indicate that MDMX functions as a regulator of MDM2. Copyright (C) 1999 Federation of European Biochemical Societies.

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MDM2 interacts with MDMX through their RING finger domains

Abstract

Keywords

ASJC Scopus subject areas

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