PMID- 10094408
OWN - NLM
STAT- MEDLINE
DCOM- 19990429
LR  - 20181113
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 191
IP  - 1-2
DP  - 1999 Jan
TI  - Protein kinase CK2-dependent regulation of p53 function: evidence that the
      phosphorylation status of the serine 386 (CK2) site of p53 is constitutive and
      stable.
PG  - 187-99
AB  - The p53 tumour suppressor protein is regulated by several mechanisms including
      multisite phosphorylation. One of the protein kinases which has an established
      role in regulating p53 function is the protein kinase CK2. The regulation by CK2 
      occurs both through interaction of p53 with CK2 itself (the regulatory beta
      subunit) and phosphorylation at the penultimate residue of p53, serine 386
      (murine p53). Strikingly, this phosphorylation event controls several independent
      functions of p53 including site-specific DNA binding, strand renaturation,
      transcriptional repression and the anti-proliferative function of p53. However,
      CK2 is a constitutively-active enzyme and therefore the mechanism by which the
      phosphorylation of p53 at serine 386 is itself regulated, or indeed the question 
      as to whether phosphorylation of this site is regulated at all, remains
      unresolved. In this paper we provide evidence that serine 386 is highly resistant
      to dephosphorylation in cultured cells, even though this site can be
      dephosphorylated in vitro by recombinant protein phosphatase 1. These data
      suggest that, once phosphorylated at the CK2 site, a p53 molecule remains in this
      modified form throughout its lifespan. To address the issue of whether the level 
      of serine 386 phosphorylation may be regulated through controlling the
      subcellular compartmentalisation of p53 and CK2, we examined the subcellular
      localisation of p53 and CK2alpha in C57MG cells and Rat-1 fibroblasts by
      immunofluorescence staining. Both proteins were present in the cytoplasm and
      enriched in the nucleus, with minor variations in the intensity of subcellular
      location over the course of the cell cycle. Similarly, activation of p53 by UV
      irradiation or DNA damage-inducing drugs had no effect on either the localisation
      or levels of CK2alpha, even although significant nuclear p53 accumulation was
      observed. A striking observation arising from these studies was the intense
      staining of CK2alpha with the centrosomes, suggesting a potentially important
      role for this kinase in microtubule formation and/or chromosomal segregation.
FAU - McKendrick, L
AU  - McKendrick L
AD  - Biomedical Research Centre, Ninewells Hospital and Medical School, The University
      of Dundee, UK.
FAU - Milne, D
AU  - Milne D
FAU - Meek, D
AU  - Meek D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Casein Kinase II
MH  - Cell Cycle
MH  - Cell Line
MH  - Centrosome/enzymology
MH  - DNA Damage
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Rats
MH  - Serine/*metabolism
MH  - Subcellular Fractions/enzymology/metabolism
MH  - Tumor Suppressor Protein p53/chemistry/*metabolism
EDAT- 1999/03/27 00:00
MHDA- 1999/03/27 00:01
CRDT- 1999/03/27 00:00
PHST- 1999/03/27 00:00 [pubmed]
PHST- 1999/03/27 00:01 [medline]
PHST- 1999/03/27 00:00 [entrez]
PST - ppublish
SO  - Mol Cell Biochem. 1999 Jan;191(1-2):187-99.