Tumour suppressor protein p53 released by nuclease digestion increases at the onset of rat liver regeneration

Francesc Miro, Jean-Claude Lelong, Floria Pancetti, Nerea Roher, Arlette Duthu, Maria Plana, Jean Christophe Bourdon, Oriol Bachs, Evelyne May, Emilio Itarte

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    Abstract

    Background/Aims: Protein kinase CK2 (CK2) increases when cells are committed to proliferate, as in liver regeneration, This enzyme phosphorylates the tumour suppressor protein p53, whose expression controls the levels of many other cell cycle proteins. The aim of this study was to determine if CK2 was affected by p53.

    Methods: Male Sprague-Dawley rats (200-250 g) were subjected to either partial hepatectomy or laparotomy and the levels and subcellular distribution of p53 were studied, following the approach used earlier for CK2. The levels of both proteins were also studied in the human cell lines HL-60 (devoid of p53) and HepG2 (with normal p53 levels) and in fibroblasts from transgenic p53-deficient mice (p53-/-) or homozygous for wild-type p53 (p53+/+), Computer-assisted search was used to detect p53 consensus sequences in genes for CK2 submits, Binding of p53 protein to some of these sequences was assayed by electrophoretic mobility shift assay.

    Results: Rat liver p53 protein was present mainly in the fraction extracted from intact nuclei by nucleases (S1) and showed a transient increase, at 6 h post partial hepatectomy, as observed previously with nuclear CK2, The human CK2 alpha gene presents the consensus sequence for trans-activation by p53 and specific binding of p53 protein to some of these sequences was detected in vitro. Total CR2 alpha was higher in HepG2 than in HL-60 cells but total CK2 and its cytosolic/ nuclear distribution was similar in mice (p53+/+) fibroblasts and (p53-/-) fibroblasts.

    Conclusions: p53 is present in the nuclease-extracted S1 fraction from liver cells, as described for CK2, and undergoes similar changes at the beginning of rat liver regeneration. However, the data on cultured cells suggest that the expression of CK2 and its subcellular localization are p53-independent events.

    Original languageEnglish
    Pages (from-to)306-314
    Number of pages9
    JournalJournal of Hepatology
    Volume31
    Issue number2
    Publication statusPublished - 1999

    Cite this

    Miro, F., Lelong, J-C., Pancetti, F., Roher, N., Duthu, A., Plana, M., Bourdon, J. C., Bachs, O., May, E., & Itarte, E. (1999). Tumour suppressor protein p53 released by nuclease digestion increases at the onset of rat liver regeneration. Journal of Hepatology, 31(2), 306-314. http://www.jhep-elsevier.com/issues#