Quantitation of a 55K cellular protein: similar amount and instability in normal and malignant mouse cells.

Mora, Peter T.; Chandrasekaran, Krish; Hoffman, John C.; McFarland, Vivian W.

doi:10.1128/mcb.2.7.763

Cited by 48 publications

(31 citation statements)

References 30 publications

(59 reference statements)

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“…p53-was undetectable in p53 -deficient UISO-MEL-6 as well as fibroblasts WS1 reflecting a short half-life of noninduced p53 in normal cells (Mora et al, 1982). In accordance with a previous immunocytochemical study (Rauth et al, 1994b), UISO-MEL-29 demonstrated low, while 8,11,16 and 23 showed high levels of p53 protein.…”

Section: Ing1csupporting

confidence: 73%

Melanoma cells can tolerate high levels of transcriptionally active endogenous p53 but are sensitive to retrovirus-transduced p53

et al. 2003

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Malignant melanomas are frequently characterized by elevated levels of wild-type p53, suggesting that p53 function could be suppressed by a mechanism different from p53 mutation. We analysed the functionality of the p53-signaling pathway in a panel of seven human melanoma cell lines consisting of one p53-deficient line, two lines with mutant p53, and four lines expressing wildtype p53. Only lines with wild-type p53 were characterized by elevated levels of endogenous p21, high activity of p53-responsive reporters and accumulation of p53 in response to genotoxic stress, common properties of functional p53. The presence of wild-type p53 was associated with depletion or loss of p14 ARF and p16 expression. The levels of p33ING1b and p24 ING1c, two major products of Ing1 locus and putative coregulators of p53, were elevated in all cell lines tested; however, ectopic expression of either ING1 isoform had no effect on cell proliferation. All lines retained expression of Apaf-1, and all but one remained sensitive to ectopic expression of retrovirus-transduced p53. Our data indicate that regardless of abnormally high levels of p53 in melanomas, their p53 remains competent in transactivation of its targets, and, if highly overexpressed, capable of growth inhibition. Hence, the p53 pathway in malignant melanomas can be considered for pharmacological targeting and anticancer gene therapy.

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Section: Ing1csupporting

confidence: 73%

Melanoma cells can tolerate high levels of transcriptionally active endogenous p53 but are sensitive to retrovirus-transduced p53

et al. 2003

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“…1, BHK Stability of p53. It has been suggested that the stability of the p53 tumor antigen might be influenced by its association with viral tumor antigens (20,22 (Fig. 2) showed, however, that the p53 protein is approximately equally stable in the two cell lines.…”

Section: Resultsmentioning

confidence: 97%

“…(22,25). It has been suggested that in SV40-transformed cells the association with T antigen is responsible for the increased stability of p53, which in turn results in an elevated concentration of this protein (20,22).…”

mentioning

confidence: 99%

Adenovirus serotype determines association and localization of the large E1B tumor antigen with cellular tumor antigen p53 in transformed cells.

Zantema¹,

Schrier²,

et al. 1985

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The distribution and stability of the cellular tumor antigen p53 were studied in baby rat kidney cells transformed by region El sequences of nononcogenic adenovirus (Ad) type 5 (Ad5) or oncogenic type 12 (Adl2). In transformed cells expressing the large ElB T antigen of AdS, p53 was associated with this T antigen. The complexed proteins were concentrated in a cytoplasmic body, which has been shown to consist of a cluster of 8-nm filaments (A. Zantema et al., Virology 142:44-58, 1985). In transformed cells expressing the EIB region of Adl2, however, no association between the viral large T antigen and p53 was detectable. In the latter case, both proteins were found almost exclusively in the nucleus. The stability of p53 in both Ad5-and Adl2-transformed cells was increased relative to that in primary cells or cells immortalized by the ElA region only. Thus, the increased stability of p53 in Ad-transformed cells is not caused by association with a viral T antigen, but it correlates with expression of E1B and with morphological transformation.

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“…7). The 3-h labeling period used here is similar to that used previously to determine the amount of p53 that accumulates in various normal and tumorigenic cells (7,37,49,50). This technique gives a good estimate of the steady-state level of p53 in cells only if the half-life of the protein is less than ca.…”

mentioning

confidence: 99%

Energy requirement for degradation of tumor-associated protein p53.

Gronostajski¹,

Goldberg²,

Pardee³

1984

Mol. Cell. Biol.

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A 53,000-dalton protein (pS3) present in large amounts in several types of tumorigenic cells was rapidly degraded in nontumorigenic BALB/c 3T3 fibroblasts (t11, -0.5 h) but not in tumorigenic methylcholanthrene-induced mouse sarcoma cells (t,,, >2 h). In 3T3 cells, dinitrophenol and 2-deoxyglucose, agents which reduce ATP production, inhibited the rapid degradation of p53 and the slower breakdown of total cell protein. After removal of these agents, the degradation of both p53 and total cell proteins resumed at their normal rates. Inhibitors of intralysosomal proteolysis (Ep475 and chloroquine) did not reduce the rate of degradation of p53. Thus, in 3T3 cells, p53 appears to be degraded by a nonlysosomal, ATP-dependent proteolytic system similar to that previously shown to degrade short-and long-lived proteins in growing fibroblasts. The immunoreactive p53 which remained in ATP-depleted cells had the same molecular weight as the p53 in the control cells. No intermediate products of p53 degradation were detected by immunoprecipitation in either ATP-depleted or control cells. Hence, ATP seems to be required for an initial step in the degradation of p53. Although the amount of labeled p53 was increased in simian virus 40-transformed and methylcholanthrene-induced mouse sarcoma cells, the amount of p53 labeled during a 3-h pulse in Moloney virus-and Rous sarcoma virus-transformed cells and untransformed 3T3 cells was similar. Thus, an increased net rate of p53 accumulation is not a common feature of transformed tumorigenic cells.Several types of tumorigenic, transformed mammalian cells contain high levels of a 53,000-dalton phosphoprotein. called p53 (31,32). By contrast, levels of p53 are 10-to 100-fold lower in untransformed fibroblasts (19,40,49,50 The half-life of p53 is less than 1 h in untransformed mouse 3T3 fibroblasts but greater than 22 h in SV40-transformed 3T3 cells (40). This greater stability presumably is responsible for the 25-to 100-fold increase in the level of p53 seen in SV40-transformed cells. In fact, the levels of translatable mRNA for p53 are similar in untransformed and SV40 transformed cells (40). In mouse F9 embryonal carcinoma cells, the half-life of p53 is approximately 3.5 h (41). Since the levels of translatable mRNA for p53 are similar in F9 and 3T3 cells, the high level of p53 found in F9 cells is also probably due to its greater stability.A characteristic feature of tumorigenic, transformed animal cells is the loss of control of cell proliferation (9,43

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Quantitation of a 55K cellular protein: similar amount and instability in normal and malignant mouse cells.

Cited by 48 publications

References 30 publications

Melanoma cells can tolerate high levels of transcriptionally active endogenous p53 but are sensitive to retrovirus-transduced p53

Melanoma cells can tolerate high levels of transcriptionally active endogenous p53 but are sensitive to retrovirus-transduced p53

Adenovirus serotype determines association and localization of the large E1B tumor antigen with cellular tumor antigen p53 in transformed cells.

Energy requirement for degradation of tumor-associated protein p53.

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