Cell Cycle‐dependent Regulation of Nuclear P53 Expression Occurs in One Subclass of Human Tumour Cells and in Untransformed Cells

David‐Pfeuty, Thérèse; Chakrani, Fatima; Ory, Katherine; Nouvian-Dooghe, Yolande

doi:10.1016/s0248-4900(97)86899-2

Cited by 20 publications

(25 citation statements)

References 35 publications

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“…The 57 kDa band represented 35% and 15% of the signal in the nuclear and cytoplasmic preparations from Rh28 cells (wtp53), respectively, and *5% of the signal in both the cytoplasmic and nuclear preparations of the Daoy cells (mp53). The identity of these bands is unknown, but similar bands have been reported with 1801 in one other study (Banks et al, 1986) and a 57 kDa band has also been reported with DO7 in a study by David-Pfeuty et al (1996). We conclude that 1801, DO1, DO7 and BP53.12 bind specifically to both wild-type and mutant p53 on immunoblots, and that 1801 cross-reacts with at least one other unidentified protein.…”

Section: Introductionsupporting

confidence: 77%

Differences in epitope accessibility of p53 monoclonal antibodies suggest at least three conformations or states of protein binding of p53 protein in human tumor cell lines

et al. 1998

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The p53 tumor suppressor gene is deleted or mutated in over 50% of human tumors. Mutations frequently extend the halflife of the p53 protein; and a high level of nuclear p53 expression, detected by immunohistochemistry, has been used to predict the p53 status of tumors. We compared the sensitivity and reactivity of five frequently used, commercially available monoclonal antibodies (1801, DO1, DO7, BP53.12 and 421) in immunoblot and immunofluorescence assays, and found that results differed among the antibodies. Comparison of immunoblot analysis of denatured nuclear and cytoplasmic p53 protein were consistent with antibodies DO1, DO7 and BP53.12, each of which generated a strong specific signal in both cell fractions. However, in situ analysis demonstrated that although all antibodies recognized nuclear p53, only BP53.12 and 421 recognized p53 protein in the cytoplasm. In addition, 1801 produced a signal in p53-negative tumor cell lines. Differences in situ among the antibodies were probably due to the accessibility of their respective epitopes and suggested that nuclear and cytoplasmic p53 either have different three-dimensional conformations or are bound to different proteins. A third p53 protein conformation was also suggested by the observation that only two of the five antibodies (BP53.12 and DO7) detected induced levels of p53 in situ following exposure to ionizing radiation. In summary, except for the fact that DO7 does not recognize cytoplasmic p53 in situ, we found it to be the most specific, versatile, and reliable antibody. We conclude that the p53 antibody of choice depends upon the specific goal of a study and the method used to detect this protein.

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Section: Introductionsupporting

confidence: 77%

Differences in epitope accessibility of p53 monoclonal antibodies suggest at least three conformations or states of protein binding of p53 protein in human tumor cell lines

et al. 1998

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“…17 In addition, nuclear p53 has only been detected in untransformed cells at the G 1 /S transition, while cytoplasmic p53 is associated with S phase cells, and cells expressing high levels of cyclin A. 18 The striking similarity of the timing between p21 Waf1/Cip1 and E2F expression is consistent with the notion that E2F/p53 interactions play a role in regulating the transcriptional activity of p53 throughout the cell cycle. Hence, by binding and retaining Ser315 phosphorylated p53 in the nucleus, E2F1-3 act as fine tuners for p53 during cell cycle progression.…”

Section: The E2f Familymentioning

confidence: 65%

Some p53-binding proteins that can function as arbiters of life and death

2006

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Four sets of p53-binding proteins are discussed in this review. These are the E2F family, the ASPP family, Y-boxbinding protein YB1, and the prolyl isomerase Pin1. Each appears to play a role in the decision by p53 to induce an arrest of cell proliferation or apoptosis and they may also be independent markers of cancer. Their activities appear to be linked with the cell cycle and they may also interact with each other. In this review, the properties of each protein class are discussed as well as how they affect p53 functions. A model is proposed as to how their activities might be coordinated.

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“…Nuclear accumulation of wt p53 is restricted to G1 phase in a number of normal ®broblastic and epithelial cells and in wt p53-expressor tumor-derived MCF-7 cells (Shaulsky et al, 1990;Takahashi and Suzuki, 1994;David-Pfeuty et al, 1996). Such a cell cycle restraint, however, is abolished upon exposure to most wt p53-activating, stress signals (for review, see Jimenez et al, 1999).…”

Section: Reversible Induction Of Wt P53 Nuclear Accumulation and Of Nmentioning

confidence: 99%

Common and reversible regulation of wild-type p53 function and of ribosomal biogenesis by protein kinases in human cells

et al. 2001

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Two speci®c inhibitors of cyclin-dependent kinase 2 (Cdk2), roscovitine and olomoucine, have been shown recently to induce nuclear accumulation of wt p53 and nucleolar unravelling in interphase human untransformed IMR-90 and breast tumor-derived MCF-7 cells. Here, we show that the early response of MCF-7 cells to roscovitine is fully reversible since a rapid restoration of nucleolar organization followed by an induction of p21 WAF1/CIP1 , a downregulation of nuclear wt p53 and normal cell cycle resumption occurs if the compound is removed after 4 h. Interestingly, similar reversible e ects are also induced by the casein kinase II (CKII) inhibitor, 5,6-dichloro-1-b-D-ribofuranosylbenzimidazole. Upon short-term treatment also, both compounds signi®cantly, but reversibly, reduce the level of 45S precursor ribosomal RNA. Cells exposed to the two types of protein kinase inhibitors for longer times keep exhibiting altered nucleolar and wt p53 features, yet they strikingly di erentiate in that most roscovitine-treated cells fail to ever accumulate high levels of p21 WAF1/CIP1 in contrast with DRB-treated ones. In both cases, however, the cells eventually fall into an irreversible state and die. Moreover, we found that constitutive overexpression of p21 WAF1/CIP1 alters the nucleolar unravelling process in the presence of DRB, but not of roscovitine, suggesting a role for this physiological Cdk inhibitor in the regulation of nucleolar function. Our data also support the notion that both roscovitine-and DRB-sensitive protein kinases, probably including Cdk2 and CKII, via their dual implication in the p53-Rb pathway and in ribosomal biogenesis, would participate in coupling cell growth with cell division. Oncogene (2001) 20, 5951 ± 5963.

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Cell Cycle‐dependent Regulation of Nuclear P53 Expression Occurs in One Subclass of Human Tumour Cells and in Untransformed Cells

Cited by 20 publications

References 35 publications

Differences in epitope accessibility of p53 monoclonal antibodies suggest at least three conformations or states of protein binding of p53 protein in human tumor cell lines

Differences in epitope accessibility of p53 monoclonal antibodies suggest at least three conformations or states of protein binding of p53 protein in human tumor cell lines

Some p53-binding proteins that can function as arbiters of life and death

Common and reversible regulation of wild-type p53 function and of ribosomal biogenesis by protein kinases in human cells

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