Pseudophosphatase MK-STYX Alters Histone Deacetylase 6 Cytoplasmic Localization, Decreases Its Phosphorylation, and Increases Detyrosination of Tubulin

Autor: Shantá D. Hinton, Dallas A. Banks, Emily S Pickering, Kirstin M. Reed, Alexys T Riddick, Ashley M. Zhang, Yuming Cao, Andrew M. Mattei
Rok vydání: 2019
Předmět:
Fluorescent Antibody Technique
Histone Deacetylase 6
lcsh:Chemistry
chemistry.chemical_compound
Cytosol
0302 clinical medicine
Tubulin
Phosphorylation
lcsh:QH301-705.5
Spectroscopy
0303 health sciences
biology
General Medicine
Computer Science Applications
Cell biology
Protein Transport
030220 oncology & carcinogenesis
HDAC6 (histone deacetylase isoform 6)
Protein Binding
pseudophosphatase
Article
Catalysis
Cell Line
microtubules
Inorganic Chemistry
Protein Aggregates
03 medical and health sciences
Stress granule
Detyrosination
Humans
Physical and Theoretical Chemistry
Protein kinase A
Molecular Biology
030304 developmental biology
Cell Nucleus
Organic Chemistry
Tyrosine phosphorylation
MK-STYX (MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein)
lcsh:Biology (General)
lcsh:QD1-999
post-translational modification
chemistry
Acetylation
biology.protein
Tyrosine
Histone deacetylase
Apoptosis Regulatory Proteins
Protein Processing
Post-Translational
Biomarkers
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 6
International Journal of Molecular Sciences, Vol 20, Iss 6, p 1455 (2019)
ISSN: 1422-0067
DOI: 10.3390/ijms20061455
Popis: The catalytically inactive mitogen-activated protein (MAP) kinase phosphatase, MK-STYX (MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein) interacts with the stress granule nucleator G3BP-1 (Ras-GAP (GTPase-activating protein) SH3 (Src homology 3) domain-binding protein-1), and decreases stress granule (stalled mRNA) formation. Histone deacetylase isoform 6 (HDAC6) also binds G3BP-1 and serves as a major component of stress granules. The discovery that MK-STYX and HDAC6 both interact with G3BP-1 led us to investigate the effects of MK-STYX on HDAC6 dynamics. In control HEK/293 cells, HDAC6 was cytosolic, as expected, and formed aggregates under conditions of stress. In contrast, in cells overexpressing MK-STYX, HDAC6 was both nuclear and cytosolic and the number of stress-induced aggregates significantly decreased. Immunoblots showed that MK-STYX decreases HDAC6 serine phosphorylation, protein tyrosine phosphorylation, and lysine acetylation. HDAC6 is known to regulate microtubule dynamics to form aggregates. MK-STYX did not affect the organization of microtubules, but did affect their post-translational modification. Tubulin acetylation was increased in the presence of MK-STYX. In addition, the detyrosination of tubulin was significantly increased in the presence of MK-STYX. These findings show that MK-STYX decreases the number of HDAC6-containing aggregates and alters their localization, sustains microtubule acetylation, and increases detyrosination of microtubules, implicating MK-STYX as a signaling molecule in HDAC6 activity.
Databáze: OpenAIRE
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