The Organization and Expression of themdm2Gene

Luna, Roberto Montes de Oca; Tabor, A; Eberspaecher, Heidi; Hulboy, Diana L.; Worth, Laura L.; Colman, Michael S.; Finlay, Cathy A.; Lozano, Guillermina

doi:10.1006/geno.1996.0210

Cited by 42 publications

(29 citation statements)

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“…Preliminary information can be collected from expression studies or experiments with in vitro di erentiation models. A ubiquitous low level expression pattern was found throughout mouse embryonic development (Montes de Oca Luna et al, 1996) Restricted and reproducible expression patterns of Mdm2 were detected at particular stages of zebra®sh development (B Thisse, C Thisse and JP, unpublished results). These contrasting observations could possibly be reconciled by the recent proposal of an antiteratogenic function for p53 during development (Nicol et al, 1995;MacCallum et al, 1996;Hall and Lane, 1997).…”

Section: The P53-mdm2 Feedback Loop In Developmentmentioning

confidence: 93%

“…Several alternatively spliced transcripts were detected in transformed cell lines or tumors, some of them giving rise also to proteins having lost the ability to bind p53 Maxwell, 1994;Sigalas et al, 1996). However, no evidence was found for their existence in normal physiological situations (Montes de Oca Luna et al, 1996). Thus, N-terminally truncated forms may be produced by internal translational initiations or alternative splicing events, but may occur less frequently in normal physiological situations than in tumors or transformed cell lines.…”

Section: Mdm2 Gene Structure and Expressionmentioning

confidence: 98%

“…The mouse gene contains at least 12 exons spread over about 25 kb of DNA (Montes de Oca Luna et al, 1996;Jones et al, 1996). Two promoters were characterized: the ®rst one is located upstream of the gene and is expressed constitutively whereas the second one is present in the ®rst intron and is controlled by p53 in both mouse and human through two adjacent p53 binding sites (Wu et al, 1993;Juven et al, 1993;Barak et al, 1994;Zauberman et al, 1995).…”

Section: Mdm2 Gene Structure and Expressionmentioning

confidence: 99%

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Mdm2: keeping p53 under control

1997

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The Mdm2 gene is overexpressed in several human tumors. The oncogenic potential of Mdm2 is partially explained by the inhibition of the activity of the tumor suppressor protein p53. Determination of the threedimensional structure of complexes between Mdm2 and the N-terminal p53 peptide provided a molecular basis for the inhibition of the transcriptional function of p53 by Mdm2. More dramatically, p53 is targeted by Mdm2 for rapid degradation. The Mdm2 gene itself is activated by p53, which gives the opportunity for feed-back control of p53 activity. Keeping p53 under control is most likely the major task of Mdm2 during early development. Recently, evidence was provided for an alternative, p53-independent function of Mdm2.

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Section: The P53-mdm2 Feedback Loop In Developmentmentioning

confidence: 93%

Section: Mdm2 Gene Structure and Expressionmentioning

confidence: 98%

Section: Mdm2 Gene Structure and Expressionmentioning

confidence: 99%

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Mdm2: keeping p53 under control

1997

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“…This cDNA has three amino acid changes compared to the initially published MDM2 sequence (Fakharzadeh et al, 1991;Dubs-Poterszman et al, 1995;Montes de Oca Luna et al, 1996;203 T to S, 419 H to D and 486 S to T). The 5' end of the cDNA was modi®ed to improve the translation eciency by introducing the rabbit b-globin leader sequence.…”

Section: Construction Of the Hcmv-mdm2 Expression Vectormentioning

confidence: 98%

“…The transforming properties of MDM2 were established in transfections with the mdm2 gene (Fakharzadeh et al, 1991;Finlay, 1993), which produces RNAs with dierent coding potential (Barak et al, 1994;Haines et al, 1994;Maxwell, 1994;Olson et al, 1993;BuesoRamos et al, 1995BuesoRamos et al, , 1996. Spliced RNAs are expressed at higher levels in tumours and cell lines compared to normal tissues (Sigalas et al, 1996;Montes de Oca Luna et al, 1996). Some tumours contain MDM2 with mutations in the zinc ®nger (Schlott et al, 1997).…”

Section: Mdm2 and Tumorigenesismentioning

confidence: 99%

MDM2 overexpression generates a skin phenotype in both wild type and p53 null mice

et al. 1999

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The MDM2 proto-oncogene is overexpressed in human tumours and regulates the activities of the tumour suppressors p53 and pRB. We created mice that overexpress MDM2 under the control of the CMV promoter. These mice did not display an increased tumour incidence, but rather a speci®c skin phenotype, characterized by desquamation and hyperkeratosis. Transgenic MDM2 was found to be overexpressed in the epidermis, a tissue that normally expresses high levels of MDM2. The phenotype appeared during the ®rst week after birth and then lessened with age, closely following the level of expression of the transgene. MDM2 overexpression was associated with an increase in proliferation in the basal layer, thickening of the epidermis, altered expression of the dierentiation markers cytokeratin CK14, CK10 and CK1, and a decrease in the size and the number of granules that contain products of dierentiation. Transgenic mice on a p53 null background displayed similar although not identical changes, showing that the eects of MDM2 are to a certain degree p53 independent. The skin is a major site of MDM2 expression in mice, raising the possibility that MDM2 overexpression perturbs the normal pattern of MDM2 expression and inhibits dierentiation of the epidermis.

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