• Home
  • Search Results
  • PERP expression stabilizes active p53 via modulation of p53-MDM2 interaction in uveal melanoma cells.

PERP expression stabilizes active p53 via modulation of p53-MDM2 interaction in uveal melanoma cells.

Cell death & disease (2011-04-01)
L Davies, D Spiller, M R H White, I Grierson, L Paraoan
ABSTRACT

The activation and regulation of target genes by the tumour-suppressor p53 dictates the fate of a cell, with cell cycle arrest or apoptosis being two distinct outcomes. PERP (p53 apoptosis effector related to PMP-22), a p53 transcriptional target, is induced specifically during apoptosis but not cell cycle arrest. Downregulation of PERP is associated with the aggressive, monosomy 3-type of uveal melanoma (UM), the most common primary intraocular tumour in adults, and increased PERP expression has a pro-apoptotic effect in UM cells. Here, we identify a novel effect of PERP expression, as elevated PERP protein positively influences active levels of its own transcriptional regulator, p53. Using fluorescent fusion proteins of PERP, p53 and MDM2, we demonstrate in single living UM cells that PERP expression significantly enhances p53 activity and its nuclear localization, increases p53-dependent transcription (including that of MDM2) while allowing oscillatory nucleo-cytoplasmic shuttling of p53/MDM2 complexes. Phosphorylation of p53 serine residues that interfere with the interaction between p53 and its negative regulator MDM2 and enhance pro-apoptotic gene transcription also occurs subsequent to PERP expression. These results implicate a role for PERP in amplifying functional p53 levels that promote p53-dependent apoptosis, and reveal a potential target for exploitation in enhancing p53 activity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Zinc chloride, reagent grade, ≥98%
Sigma-Aldrich
Zinc chloride, 99.999% trace metals basis
Sigma-Aldrich
Zinc chloride, anhydrous, powder, ≥99.995% trace metals basis
Sigma-Aldrich
GeneJuice® Transfection Reagent, Non-lipid based chemical transfection reagent optimized for maximum transfection efficiency, ease-of-use, and minimal cytotoxicity on a wide variety of mammallian cells.
Sigma-Aldrich
Zinc chloride, BioReagent, for molecular biology, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Zinc chloride, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥98%
Sigma-Aldrich
Zinc chloride, ACS reagent, ≥97%
Sigma-Aldrich
Zinc chloride, puriss., meets analytical specification of Ph. Eur., BP, USP, 98-100.5%
Sigma-Aldrich
Zinc chloride, AnhydroBeads, amorphous, −10 mesh, 99.99% trace metals basis
Sigma-Aldrich
Zinc chloride, AnhydroBeads, amorphous, −10 mesh, 99.999% trace metals basis
Sigma-Aldrich
Anti-MDM2 Antibody, clone 2A10, clone 2A10, from mouse
Sigma-Aldrich
Anti-p53 (pantropic) Antibody, clone DO-1, clone DO-1, from mouse

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.