Accumulation of wild-type p53 protein in progressive multifocal leukoencephalopathy: a flow of cytometry and DNA sequencing study.
p52 protein accumulation in JC virus (JCV)-infected cells of progressive multifocal leukoencephalopathy (PML) has been previously shown. Since many viral proteins are known to bind and stabilize p53, we are addressing the question of whether p53 protein accumulation in PML is the result of its sequestration by JCV and not the outcome of a p53 gene mutation which would prolong its half-life. We have investigated the status of the p53 gene in frozen autopsy brain samples from five PML patients. After isolating genomic DNA, p53 gene exons 2 through 9 were amplified and sequenced. No discrepancies were found in the DNA sequences of exons 2 through 9 and their intron/exon barriers when compared to those published for wild-type p53. On the other hand, dual (p53/DNA) flow cytometry analysis revealed p53 expression above that of the isotypic controls for each case. No aneuploid populations could be identified, however, which seems at odds with the aneuploid status normally associated with mutation-induced p53 dysfunction. These results indicate that the p53 gene harbors no mutations in PML and provide further evidence of p53 protein accumulation in this condition. Since p53 protein buildup in JCV-infected cells is not the consequence of a mutagenic interaction between JCV and the cell genome, we propose instead that p53 accumulation results from its binding and stabilization by JCV T protein.
Ariza
A
A
Department of Pathology, Hospital Germans Trias i Pujol, Autonomous University of Barcelona, Spain.
von Uexküll-Güldeband
C
C
Mate
J L
JL
Isamat
M
M
Aracil
C
C
Cruz-Sánchez
F F
FF
Navas-Palacios
J J
JJ
D001483:Base Sequence; D015342:DNA Probes; D005434:Flow Cytometry; D006801:Humans; D017403:In Situ Hybridization; D007968:Leukoencephalopathy, Progressive Multifocal / Q000473:pathology*; D008969:Molecular Sequence Data; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D015342:DNA Probes; D016159:Tumor Suppressor Protein p53