Bacterial Growth Inhibition Screen (BGIS) identifies a loss‐of‐function mutant of the DEK oncogene, indicating DNA modulating activities of DEK in chromatin

The DEK oncoprotein regulates cellular chromatin function via a number of protein–protein interactions. However, the biological relevance of its unique pseudo‐SAP/SAP‐box domain, which transmits DNA modulating activities in vitro, remains largely speculative. As hypothesis‐driven mutations failed to...

Full description

Saved in:

Bibliographic Details
Published in:	FEBS letters Vol. 595; no. 10; pp. 1438 - 1453
Main Authors:	Guo, Haihong, Prell, Malte, Königs, Hiltrud, Xu, Nengwei, Waldmann, Tanja, Hermans‐Sachweh, Benita, Ferrando‐May, Elisa, Lüscher, Bernhard, Kappes, Ferdinand
Format:	Journal Article
Language:	English
Published:	England 01-05-2021
Subjects:	Bias Cell Nucleus - drug effects Cell Size - drug effects chromatin Chromatin - chemistry Chromatin - genetics Chromatin - metabolism Chromosomal Proteins, Non-Histone - chemistry Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - metabolism Chromosomal Proteins, Non-Histone - toxicity DEK DNA - metabolism Escherichia coli Escherichia coli - drug effects Escherichia coli - genetics Escherichia coli - growth & development Gene Expression Regulation, Bacterial - drug effects Genome, Bacterial - drug effects Genome, Bacterial - genetics Humans Loss of Function Mutation Mutagenesis Nucleosomes - chemistry Nucleosomes - genetics Nucleosomes - metabolism oncogene Oncogene Proteins - chemistry Oncogene Proteins - genetics Oncogene Proteins - metabolism Oncogene Proteins - toxicity Peptide Fragments - chemistry Peptide Fragments - genetics Peptide Fragments - metabolism Peptide Fragments - toxicity Poly-ADP-Ribose Binding Proteins - chemistry Poly-ADP-Ribose Binding Proteins - genetics Poly-ADP-Ribose Binding Proteins - metabolism Poly-ADP-Ribose Binding Proteins - toxicity protein domain Protein Domains - genetics protein function recombinant protein toxicity Recombinant Proteins - chemistry Recombinant Proteins - genetics Recombinant Proteins - metabolism Recombinant Proteins - toxicity SAP domain Toxicity Tests - methods protein domain Escherichia coli protein function DEK SAP domain recombinant protein toxicity chromatin oncogene
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The DEK oncoprotein regulates cellular chromatin function via a number of protein–protein interactions. However, the biological relevance of its unique pseudo‐SAP/SAP‐box domain, which transmits DNA modulating activities in vitro, remains largely speculative. As hypothesis‐driven mutations failed to yield DNA‐binding null (DBN) mutants, we combined random mutagenesis with the Bacterial Growth Inhibition Screen (BGIS) to overcome this bottleneck. Re‐expression of a DEK‐DBN mutant in newly established human DEK knockout cells failed to reduce the increase in nuclear size as compared to wild type, indicating roles for DEK–DNA interactions in cellular chromatin organization. Our results extend the functional roles of DEK in metazoan chromatin and highlight the predictive ability of recombinant protein toxicity in E. coli for unbiased studies of eukaryotic DNA modulating protein domains.
Bibliography:	Edited by Claus Azzalin
ISSN:	0014-5793 1873-3468
DOI:	10.1002/1873-3468.14070