Cellular adhesion regulates p53 protein levels in primary human keratinocytes.
To gain insight into p53 tissue-specific regulatory pathways and biological activities, we investigated mechanisms that may account for the elevated levels of p53 protein in human foreskin keratinocytes, relative to levels in dermal fibroblasts in vitro. Here, we report that the loss of cell anchorage resulted in an approximately 5-fold decrease in p53 levels in keratinocytes, which was reversible upon reattachment of cells to a substratum. In contrast, fibroblasts did not exhibit such adhesion-dependent regulation of p53 protein. Furthermore, p53 function was attenuated in keratinocytes relative to fibroblasts. These results link p53 to cell adhesion pathways and may provide a molecular basis for epigenetic differences in the maintenance of genomic stability among normal cell types.
Nigro
J M
JM
Department of Pathology, University of California, San Francisco, 94143-0506, USA.
Aldape
K D
KD
Hess
S M
SM
Tlsty
T D
TD
D002448:Cell Adhesion / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2