Phosphorylation of Serine 303 Is a Prerequisite for the Stress-Inducible SUMO Modification of Heat Shock Factor 1

Autor: Andrey Mikhailov, Lila Pirkkala, Ville Hietakangas, Niko M. Sahlberg, Johanna K. Ahlskog, Carina I. Holmberg, Lea Sistonen, Jorma J. Palvimo, Maria Hellesuo, Annika M. Jakobsson
Rok vydání: 2003
Předmět:
Transcription
Genetic
Recombinant Fusion Proteins
Molecular Sequence Data
SUMO-1 Protein
Lysine
SUMO protein
macromolecular substances
Biology
environment and public health
Phosphorylation cascade
03 medical and health sciences
0302 clinical medicine
Stress granule
Heat Shock Transcription Factors
Heat shock protein
Serine
Humans
HSP70 Heat-Shock Proteins
Amino Acid Sequence
Phosphorylation
Heat shock
HSF1
Ubiquitins
Molecular Biology
030304 developmental biology
Cell Nucleus
Transcriptional Regulation
0303 health sciences
Binding Sites
Sequence Homology
Amino Acid
fungi
Cell Biology
Cell biology
DNA-Binding Proteins
enzymes and coenzymes (carbohydrates)
Biochemistry
030220 oncology & carcinogenesis
Mutagenesis
Site-Directed
K562 Cells
Protein Processing
Post-Translational
Heat-Shock Response
Transcription Factors
Zdroj: Molecular and Cellular Biology. 23:2953-2968
ISSN: 1098-5549
DOI: 10.1128/mcb.23.8.2953-2968.2003
Popis: The heat shock response, which is accompanied by a rapid and robust upregulation of heat shock proteins (Hsps), is a highly conserved protection mechanism against protein-damaging stress. Hsp induction is mainly regulated at transcriptional level by stress-inducible heat shock factor 1 (HSF1). Upon activation, HSF1 trimerizes, binds to DNA, concentrates in the nuclear stress granules, and undergoes a marked multisite phosphorylation, which correlates with its transcriptional activity. In this study, we show that HSF1 is modified by SUMO-1 and SUMO-2 in a stress-inducible manner. Sumoylation is rapidly and transiently enhanced on lysine 298, located in the regulatory domain of HSF1, adjacent to several critical phosphorylation sites. Sumoylation analyses of HSF1 phosphorylation site mutants reveal that specifically the phosphorylation-deficient S303 mutant remains devoid of SUMO modification in vivo and the mutant mimicking phosphorylation of S303 promotes HSF1 sumoylation in vitro, indicating that S303 phosphorylation is required for K298 sumoylation. This finding is further supported by phosphopeptide mapping and analysis with S303/7 phosphospecific antibodies, which demonstrate that serine 303 is a target for strong heat-inducible phosphorylation, corresponding to the inducible HSF1 sumoylation. A transient phosphorylation-dependent colocalization of HSF1 and SUMO-1 in nuclear stress granules provides evidence for a strictly regulated subnuclear interplay between HSF1 and SUMO.
Databáze: OpenAIRE
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