Trophoblastic p53 is stabilised by a cis-trans isomerisation necessary for the formation of high molecular weight complexes involving the N-terminus of p53

Cohen, Marie-Benoîte; Wuillemin-Rambosson, Christine Gabrielle; Bischof, Paul

doi:10.1016/j.biochi.2008.02.006

Scientific article

English

Trophoblastic p53 is stabilised by a cis-trans isomerisation necessary for the formation of high molecular weight complexes involving the N-terminus of p53

Contributors

Cohen, Marie-Benoîte

; Wuillemin-Rambosson, Christine Gabrielle; Bischof, Paul

Published in

Biochimie, vol. 90, no. 6, p. 855-862

Publication date

2008

Abstract

P53 is a transcription factor also called the "cellular gatekeeper of genome" because it can induce cell cycle arrest in G1, apoptosis or affect DNA replication in response to DNA damage. Wild type p53 is localised in both the cytoplasm and nucleus of first trimester trophoblastic cells (CTB). Immunoblotting of CTB with different p53 antibodies led us to suggest that the N-terminus of p53 could be involved in the formation of high molecular weight complexes (HMWC), leading to the stabilisation of p53 in these cells. Here, we demonstrate that the N-terminus of p53 is involved in the formation of HMWC. Post-translational modifications of p53 seem to be responsible for its stabilisation and inactivation in CTB. We demonstrate that cis-trans isomerisation of proteins by the prolyl isomerase Pin1 is indispensable for the formation of these HMWC and stabilisation of p53. In contrast to observations made in other cells, in CTB, interaction of Pin1 and p53 does not involve phosphorylation of residues ser33, thr81 and ser315 of p53; on the contrary, phosphorylation of p53 leads to the rapid disappearance of some HMWC and destabilises p53. Moreover, decreasing HMWC or inhibiting Pin1 activity increases p53 activity towards its target genes MMP-9 and MMP-2, thus confirming the role of Pin-1 and these HMWC in the regulation of trophoblast invasiveness.

Keywords

Cell Movement
Humans
Isomerism
Matrix Metalloproteinases/metabolism
Molecular Weight
Peptidylprolyl Isomerase/metabolism
Protein Processing, Post-Translational
Trophoblasts/enzymology/physiology
Tumor Suppressor Protein p53/chemistry/metabolism

UNIGE affiliation entities

Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

UNIGE research groups

Laboratoire de biologie des tumeurs gynécologiques et du développement (927)

Citation (ISO format)

COHEN, Marie-Benoîte, WUILLEMIN-RAMBOSSON, Christine Gabrielle, BISCHOF, Paul. Trophoblastic p53 is stabilised by a cis-trans isomerisation necessary for the formation of high molecular weight complexes involving the N-terminus of p53. In: Biochimie, 2008, vol. 90, n° 6, p. 855–862. doi: 10.1016/j.biochi.2008.02.006

Article (Accepted version)

Identifiers

PID : unige:906
DOI : 10.1016/j.biochi.2008.02.006
PMID : 18316040

Journal ISSN

0300-9084

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Creation

24/02/2009 14:07:00

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24/02/2009 14:07:00

Update

14/03/2023 15:00:58

Status update

14/03/2023 15:00:58

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29/10/2024 11:11:51

Trophoblastic p53 is stabilised by a cis-trans isomerisation necessary for the formation of high molecular weight complexes involving the N-terminus of p53

Contributors

Published in

Publication date

Abstract

Keywords

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

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Journal ISSN

Technical informations

Creation

First validation

Update

Status update

Last indexation