The 55 kDa regulatory subunit of protein phosphatase 2A plays a role in the activation of the HPV16 long control region in human cells with a deletion in the short arm of chromosome 11.
Previous results indicated that SV40 small t is essential for SV40-induced transformation of diploid cells but dispensable for the transformation of cells with a deletion on the short arm of chromosome 11 (del-11 cells). From these results we concluded that del-11 cells contain a cellular 'SV40 small t-like' factor, which is able to transactivate the HPV16 long control region (LCR) and to complement SV40 large T in transformation. Since SV40 small t and the regulatory 55 kDa subunit (PR55) of protein phosphatase 2A (PP2A), have been shown to inhibit the enzyme activity of PP2A, the PR55 beta subunit could be the putative 'small t-like' factor. In accordance with this hypothesis, we show that the PR55 beta subunit is highly expressed in del-11 but not in diploid cells and is able to trans-activate the HPV16 LCR in diploid cells. Moreover, inhibition of PP2A by okadaic acid resulted in trans-activation of the HPV16 LCR in diploid cells. Alignment of PR55 and SV40 small t showed a common four amino acid motif DKGG. We present evidence that the integrity of this motif is necessary for the PP2A-mediated ability of SV40 small t to trans-activate the HPV16 LCR.
Smits
P H
PH
Department of Medical Microbiology, University of Amsterdam, The Netherlands.
Smits
H L
HL
Minnaar
R P
RP
Hemmings
B A
BA
Mayer-Jaekel
R E
RE
Schuurman
R
R
van der Noordaa
J
J
ter Schegget
J
J
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002880:Chromosomes, Human, Pair 11; D004171:Diploidy; D004742:Enhancer Elements, Genetic; D004988:Ethers, Cyclic / Q000494:pharmacology; D017353:Gene Deletion; D005814:Genes, Viral; D006801:Humans; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D027383:Papillomaviridae / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D054648:Protein Phosphatase 2; D012333:RNA, Messenger / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics; D015533:Transcriptional Activation
D004988:Ethers, Cyclic; D012333:RNA, Messenger; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2