Protein degradation rate is the dominant mechanism accounting for the differences in protein abundance of basal p53 in a human breast and colorectal cancer cell line

Title: Protein degradation rate is the dominant mechanism accounting for the differences in protein abundance of basal p53 in a human breast and colorectal cancer cell line
Author(s): Lakatos, E
Salehi-Reyhani, S
Barclay, M
Stumpf, M
Klug, D
Item Type: Journal Article
Abstract: We determine p53 protein abundances and cell to cell variation in two human cancer cell lines with single cell resolution, and show that the fractional width of the distributions is the same in both cases despite a large difference in average protein copy number. We developed a computational framework to identify dominant mechanisms controlling the variation of protein abundance in a simple model of gene expression from the summary statistics of single cell steady state protein expression distributions. Our results, based on single cell data analysed in a Bayesian framework, lends strong support to a model in which variation in the basal p53 protein abundance may be best explained by variations in the rate of p53 protein degradation. This is supported by measurements of the relative average levels of mRNA which are very similar despite large variation in the level of protein.
Publication Date: 10-May-2017
Date of Acceptance: 2-May-2017
URI: http://hdl.handle.net/10044/1/62746
DOI: https://dx.doi.org/10.1371/journal.pone.0177336
ISSN: 1932-6203
Publisher: Public Library of Science
Journal / Book Title: PLOS One
Volume: 12
Issue: 5
Sponsor/Funder: Engineering & Physical Science Research Council (E
Funder's Grant Number: EP/I017887/1
Copyright Statement: © 2017 Lakatos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
APPROXIMATE BAYESIAN COMPUTATION
DNA-DAMAGE
GENE-EXPRESSION
MDM2
PHOSPHORYLATION
QUANTIFICATION
Breast
Breast Neoplasms
Cell Line, Tumor
Colorectal Neoplasms
Female
Gene Expression Regulation, Neoplastic
Humans
Proteolysis
RNA, Messenger
Transcription, Genetic
Tumor Suppressor Protein p53
Breast
Cell Line, Tumor
Humans
Breast Neoplasms
Colorectal Neoplasms
RNA, Messenger
Transcription, Genetic
Gene Expression Regulation, Neoplastic
Female
Tumor Suppressor Protein p53
Proteolysis
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Article Number: e0177336
Appears in Collections:Chemistry
Biological and Biophysical Chemistry
Faculty of Natural Sciences



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