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HPMR

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MDM4, p53 regulator OKDB#: 5386
 Symbols: MDM4 Species: human
 Synonyms: HDMX, MDMX, MRP1  Locus: 1q32 in Homo sapiens


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General Comment NCBI Summary: This gene encodes a nuclear protein that contains a p53 binding domain at the N-terminus and a RING finger domain at the C-terminus, and shows structural similarity to p53-binding protein MDM2. Both proteins bind the p53 tumor suppressor protein and inhibit its activity, and have been shown to be overexpressed in a variety of human cancers. However, unlike MDM2 which degrades p53, this protein inhibits p53 by binding its transcriptional activation domain. This protein also interacts with MDM2 protein via the RING finger domain, and inhibits the latter's degradation. So this protein can reverse MDM2-targeted degradation of p53, while maintaining suppression of p53 transactivation and apoptotic functions. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2011]
General function Transcription factor
Comment
Cellular localization Nuclear
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization Oocyte
Comment
Follicle stages
Comment
Phenotypes
Mutations 1 mutations

Species: mouse
Mutation name:
type: null mutation
fertility: fertile
Comment: Loss of oocytes due to conditional ablation of Murine double minute 2 (Mdm2) gene is p53-dependent and results in female sterility. Livera G et al. (2016) Murine double minute 2 and 4 (Mdm2, Mdm4) are major p53-negative regulators, preventing thus uncontrolled apoptosis induction in numerous cell types, though their function in the female germ line has received little attention. In the present work, we have generated mice with specific invalidation of Mdm2 and Mdm4 genes in the mouse oocyte (Mdm2 (Ocko) and Mdm4 (Ocko) mice), to test their implication in survival of these germ cells. Most of the Mdm2 (Ocko) but not Mdm4 (Ocko) mice were sterile, with a dramatic reduction of the weight of ovaries and genital tract, a strong increase in FSH and LH serum levels, and a reduction of AMH serum levels. Histological analyses revealed an obvious decrease of the number of growing follicles beyond the primary stage in Mdm2(Ocko) ovaries in comparison to controls, with a pronounced increase in the apparition of primary atretic follicles, most being devoid of oocyte. Similar phenotypes were observed with Mdm2(Ocko) Mdm4(Ocko) ovaries, with no worsening of the phenotype. Whereas we failed to detect any increase of p53 level in mutant oocytes, nor any other apoptotic marker, introgression of this targeted invalidation in p53-/- mice restored the fertility of females. The present study is the first to show that Mdm2 but not Mdm4 has a critical role in oocyte survival and would be involved in premature ovarian insufficiency phenotype. This article is protected by copyright. All rights reserved.//////////////////

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created: July 6, 2016, 10:52 a.m. by: system   email:
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last update: July 6, 2016, 10:53 a.m. by: hsueh    email:



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