Abstract:
:Proteins encoded by the mdm2 gene, which has a pivotal role in the regulation of growth and differentiation, exist principally in human and murine cells as two isoforms that migrate in gels as 75-kDa and 90-kDa proteins. There is limited understanding of the respective biological roles of these isoforms, their molecular nature, and their mechanism of formation. We report here that human p75(MDM2) is an N-terminally truncated mixture of protein isoforms produced by the initiation of translation at two distinct internal AUG codons. The p75(MDM2) doublets and p90(MDM2), which is the full-length MDM2 protein, are expressed in approximately equal amounts from transcripts initiated at the constitutive P1 promoter of mdm2. Unlike murine transcripts initiated at the p53-activated P2 promoter, human cell transcripts initiated at the P2 promoter preferentially produce p90(MDM2). The ubiquitin enzyme variant protein TSG101, which interacts functionally with MDM2 in an autoregulatory loop that parallels the p53/MDM2 feedback control loop, interferes with degradation of both isoforms; however, only p90(MDM2) promotes proteolysis of TSG101 and p53. Our results reveal the mechanism of formation of the principal MDM2 isoforms, the differential effects of p53 on the production of these isoforms, and the differential abilities of human MDM2 isoforms as regulators of the MDM2/TSG101 and p53/MDM2 feedback control loops.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Cheng TH,Cohen SNdoi
10.1128/MCB.00235-06subject
Has Abstractpub_date
2007-01-01 00:00:00pages
111-9issue
1eissn
0270-7306issn
1098-5549pii
MCB.00235-06journal_volume
27pub_type
杂志文章abstract::The Saccharomyces cerevisiae Srs2 protein is involved in DNA repair and recombination. In order to gain better insight into the roles of Srs2, we performed a screen to identify mutations that are synthetically lethal with an srs2 deletion. One of them is a mutated allele of the ULP1 gene that encodes a protease specif...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.12.5130-5143.2004
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.23.8165-8174.2002
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.7.2928
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.16.6993-7002.2004
更新日期:2004-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/mcb.7.3.1101
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pub_type: 杂志文章
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更新日期:2003-03-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2001-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.8.4.1845
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.8.3164-3169.2006
更新日期:2006-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.6.2.626
更新日期:1986-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.17.6158-6169.2002
更新日期:2002-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.5.2308
更新日期:1990-05-01 00:00:00
abstract::We employed a protein gel blotting procedure to search for nuclear proteins from rat pituitary cells that bind preferentially to the 5'-flanking region of the rat prolactin gene. By gel blots of chromatin proteins from GH3 rat pituitary tumor cells with a 32P-labeled prolactin genomic clone, we detected two major bind...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.11.2967
更新日期:1985-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.11.4100
更新日期:1987-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.2660
更新日期:1990-06-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1998-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.4.1415
更新日期:1989-04-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.4.2057
更新日期:1991-04-01 00:00:00
abstract::Revertants were selected from aryl hydrocarbon hydroxylase (AHH)-deficient recessive mutants belonging to three complementation groups and from a dominant mutant of the Hepa-1 cell line. The recessive mutants had low spontaneous reversion frequencies (less than 4 X 10(-7] that were increased by mutagenesis. The majori...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.8.1597
更新日期:1984-08-01 00:00:00
abstract::The c-Myc oncoprotein (Myc) controls cell fate by regulating gene transcription in association with a DNA-binding partner, Max. While Max lacks a transcription regulatory domain, the N terminus of Myc contains a transcription activation domain (TAD) that recruits cofactor complexes containing the histone acetyltransfe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.23.10220-10234.2005
更新日期:2005-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.21.18.6170-6180.2001
更新日期:2001-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2006-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.3.1731
更新日期:1999-03-01 00:00:00
abstract::To distinguish among possible mechanisms of repair of a double-strand break (DSB) by gene conversion in budding yeast, Saccharomyces cerevisiae, we employed isotope density transfer to analyze budding yeast mating type (MAT) gene switching in G2/M-arrested cells. Both of the newly synthesized DNA strands created durin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01654-06
更新日期:2006-12-01 00:00:00