The expression of MDM2 and other p53-regulated proteins in the tissues of the developing rat.
The expression of MDM2 was monitored in tissues taken from rats at different stages of development. Two major protein species of 90K and 130K were identified, although expression was not the same in all tissues. In most the level of the larger protein tended to decrease as the foetus developed, being relatively scarce after birth. The expression of the 90K product (usually considered to be the major MDM2 protein), however, increased as the animals developed, being most abundant in adult tissues, suggesting that the two proteins play quite different roles during development. p53 expression mirrored that of the smaller MDM2 protein in most, but not all, tissues. This is consistent with previous suggestions made on the basis of in vitro studies that expression of the latter protein is regulated by p53. In addition, the level of two other p53-regulated proteins, Bcl-2 and Bax, were examined. In most tissues expression of both proteins decreased as the foetus developed, being virtually undetectable in adults. These data strongly suggest that factors other than p53 exert the major influence over Bcl-2 and Bax expression, although levels of the 90K MDM2 protein are more likely to be regulated by p53. However, it was noted that the levels of MDM2 in the tissues of p53-null mice were comparable to those seen in the normal rat.
Ibrahim
A P
AP
CRC Institute for Cancer Studies, Medical School, University of Birmingham, Edgbaston, UK.
Gallimore
P H
PH
Grand
R J
RJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D009687:Nuclear Proteins; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051736:Proto-Oncogene Proteins c-mdm2; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; C494828:Bax protein, rat; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2