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.

Smits, Paul H.M.; Smits, Henk L.; Minnaar, R. P.; Hemmings, Brian A.; Mayer-Jaekel, Regina E.; Schuurman, Rob; Noordaa, J. van der; Schegget, Jan ter

doi:10.1002/j.1460-2075.1992.tb05562.x

Cited by 39 publications

(18 citation statements)

References 45 publications

(22 reference statements)

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“…Beside the immunological aspects, there also exists experimental evidence for an intracellular surveillance mechanism negatively interfering with the expression of the viral oncogenes E6/E7 (RoÈ sl et al, 1988(RoÈ sl et al, , 1991Smits et al, 1990Smits et al, , 1992zur Hausen, 1986zur Hausen, , 1994. Monitoring viral transcription in low-grade cervical intraepithelial neoplasias by RNA/RNA in-situ-hybridization, only low abundance of E6/E7 gene expression has been observed within the basal cell layers, whereas virus-speci®c transcription was found to be uniformly elevated in undierentiated cells of specimens obtained from cancer patients (Crum et al, 1989;DuÈ rst et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Conversion of HPV 18 positive non-tumorigenic HeLa-fibroblast hybrids to invasive growth involves loss of TNF-α mediated repression of viral transcription and modification of the AP-1 transcription complex

et al. 1999

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Section: Introductionmentioning

confidence: 99%

Conversion of HPV 18 positive non-tumorigenic HeLa-fibroblast hybrids to invasive growth involves loss of TNF-α mediated repression of viral transcription and modification of the AP-1 transcription complex

et al. 1999

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“…Using the yeast two-hybrid system, McCright and Virshup demonstrated recently that, like B␣, BЈ and BЉ bind to the N-terminal domain (35). Given that they share a binding site on the A subunit, it is remarkable that there is no sequence similarity between T antigens and B subunits as there is none between the three B subunit families, except for a short stretch of four amino acids common to T antigens and B␣ (53).…”

mentioning

confidence: 99%

Separation of PP2A Core Enzyme and Holoenzyme with Monoclonal Antibodies against the Regulatory A Subunit: Abundant Expression of Both Forms in Cells

Kremmer¹,

Ohst

Kiefer

et al. 1997

Molecular and Cellular Biology

161

152

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Protein phosphatase 2A (PP2A) holoenzyme is composed of a catalytic subunit, C, and two regulatory subunits, A and B. The A subunit is rod shaped and consists of 15 nonidentical repeats. According to our previous model, the B subunit binds to repeats 1 through 10 and the C subunit binds to repeats 11 through 15 of the A subunit. Another form of PP2A, core enzyme, is composed only of subunits A and C. It is generally believed that core enzyme does not exist in cells but is an artifact of enzyme purification. To study the structure and relative abundance of different forms of PP2A, we generated monoclonal antibodies against the native A subunit. Two antibodies, 5H4 and 1A12, recognized epitopes in repeat 1 near the N terminus and immunoprecipitated free A subunit and core enzyme but not holoenzyme. Another antibody, 6G3, recognized an epitope in repeat 15 at the C terminus and precipitated only the free A subunit. Monoclonal antibodies against a peptide corresponding to the N-terminal 11 amino acids of the A␣ subunit (designated 6F9) precipitated free A subunit, core enzyme, and holoenzyme. 6F9, but not 5H4, recognized holoenzymes containing either B, B, or B؆ subunits. These results demonstrate that B subunits from three unrelated gene families all bind to repeat 1 of the A subunit, and the results confirm and extend our model of the holoenzyme. By sequential immunoprecipitations with 5H4 or 1A12 followed by 6F9, core enzyme and holoenzyme in cytoplasmic extracts from 10T1/2 cells were completely separated and they exhibited the expected specificities towards phosphorylase a and retinoblastoma peptide as substrates. Quantitative analysis showed that under conditions which minimized proteolysis and dissociation of holoenzyme, core enzyme represented at least one-third of the total PP2A. We conclude that core enzyme is an abundant form in cells rather than an artifact of isolation. The biological implications of this finding are discussed.Protein phosphatase 2A (PP2A), the most abundant serine/ threonine-specific phosphatase in mammals, plays a role in many fundamental cellular processes, including cell division (7, 30), signal transduction (36), gene expression (52), and Drosophila development (34). The PP2A holoenzyme consists of a 36-kDa catalytic C subunit and a 65-kDa regulatory A subunit, which together form the core enzyme to which one of several B subunits is bound (8, 38). The A and C subunits both exist as two isoforms (␣ and ␤) (19, 63), whereas the B subunits fall into three families called B, BЈ, and BЉ, which are unrelated to each other by protein sequence. The B family has three members, B␣, B␤, and B␥, each with a molecular mass of around 55 kDa (18,33,41); the BЈ family consists of numerous isoforms and splice variants, whose molecular masses range from 54 to 68 kDa (10, 35, 57, 69); and the BЉ family has two members, which have molecular masses of 72 and 130 kDa and are splice variants of the same gene (20). The combination of these subunits can give rise to a large number of PP2A variants, which ...

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“…PR55P, but not PR55a, could substitute the simian virus 40 small t to transactivate HPV16 LCR promotor in diploid cells (Smits et al, 1992). In rat testis, a C36p mRNA isotype (Kitagawa et al, 1990) and a specific PR55p mRNA isotype (Hatano et al, 1993) were found to be expressed specifically, suggesting a role in spermatogenesis.…”

Section: Discussionmentioning

confidence: 91%

“…Two isoforms of the PR55 subunit exist in mammals (PR55a and PR55P; Mayer et al, 1991b;Pallas et al, 1992) and in Drosophilu (DPR55-1 and DPR55-4; Mayer-Jaekel et al, 1993). Interestingly, specific physiological functions have been proposed for these distinct PR55 isoforms (Smits et al, 1992;Mayer-Jaekel et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

The PR55 and PR65 Subunits of Protein Phosphatase 2A from Xenopus laevis

Bosch

Cayla

Hoof

et al. 1995

European Journal of Biochemistry

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-EJB 95 0106/1 cDNA clones encoding the 65-kDa (PR65) and 55-kDa (PR55) regulatory subunits of protein phosphatase 2A from Xenopus laevis were isolated by homology screening with the corresponding human cDNAs, and used to analyze the developmental expression patterns of these genes. The PR65 subunit was found to be encoded by two genes, termed XPR65a and XPR65p. The open reading frames of the a and p cDNAs both span 1767 bp, and predict proteins of 64.4 kDa and 65.3 kDa, respectively, that are 87 % identical. The predicted amino acid sequence of XPR65a showed 95 % and 84% identity with human PR65a and PR65p proteins, respectively, whereas the identity of XPR65P with the same proteins was 87% and 86.5 %, respectively. Only one type of Xenopus PR55 (XPR55) was isolated that showed 93% and 84% similarity to human PR55a and PR55p, respectively. Analysis of the N-terminal region of XPR55 with the same regions of human PR55a and PR55/3, indicates that the XPR55 is the Xenopus homolog of the human PR55a isoform. Despite the overall similarity with PR55 from other species, XPR55 has an N-terminal extention of at least 24 amino acids. In the ovary, a transcript of 2.8 kb, encoding the XPR65P, was predominantly expressed and these XPR65P mRNAs are present at a constant level during oogenesis until late embryogenesis. Expression of the 2.4-kb XPR65a was low until the larval stage, then dramatically increased. In all adult tissues except ovary, the 2.4-kb a-specific mRNA was more abundant than the 2.8-kb p transcript. Two transcripts of 2.4 kb and 2.5 kb, encoding the XPR55 subunit, were detected at a constant level throughout Xenopus oogenesis and during embryogenesis. Both transcripts were also expressed at similar levels in all adult tissues, but in a tissue-specific manner. Analysis of the XPR55 and XPR65 proteins using antibodies to recombinant proteins revealed that the overall levels of the two proteins were constant, in good agreement with mRNA data.

show abstract

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.

Cited by 39 publications

References 45 publications

Conversion of HPV 18 positive non-tumorigenic HeLa-fibroblast hybrids to invasive growth involves loss of TNF-α mediated repression of viral transcription and modification of the AP-1 transcription complex

Conversion of HPV 18 positive non-tumorigenic HeLa-fibroblast hybrids to invasive growth involves loss of TNF-α mediated repression of viral transcription and modification of the AP-1 transcription complex

Separation of PP2A Core Enzyme and Holoenzyme with Monoclonal Antibodies against the Regulatory A Subunit: Abundant Expression of Both Forms in Cells

The PR55 and PR65 Subunits of Protein Phosphatase 2A from Xenopus laevis

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