Rho-kinase signaling controls nucleocytoplasmic shuttling of class IIa histone deacetylase (HDAC7) and transcriptional activation of orphan nuclear receptor NR4A1

Claudia Compagnucci; Sabina Barresi; Stefania Petrini; Enrico Bertini; Ginevra Zanni

doi:10.1016/j.bbrc.2014.12.033

Rho-kinase signaling controls nucleocytoplasmic shuttling of class IIa histone deacetylase (HDAC7) and transcriptional activation of orphan nuclear receptor NR4A1

Biochem Biophys Res Commun. 2015 Apr 3;459(2):179-183. doi: 10.1016/j.bbrc.2014.12.033. Epub 2014 Dec 12.

Authors

Claudia Compagnucci¹, Sabina Barresi¹, Stefania Petrini², Enrico Bertini¹, Ginevra Zanni³

Affiliations

¹ Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
² Research Laboratories, Confocal Microscopy Core Facility, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
³ Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. Electronic address: ginevra.zanni@opbg.net.

PMID: 25511694
DOI: 10.1016/j.bbrc.2014.12.033

Abstract

Rho-kinase (ROCK) has been well documented to play a key role in RhoA-induced actin remodeling. ROCK activation results in myosin light chain (MLC) phosphorylation either by direct action on MLC kinase (MLCK) or by inhibition of MLC phosphatase (MLCP), modulating actin-myosin contraction. We found that inhibition of the ROCK pathway in induced pluripotent stem cells, leads to nuclear export of HDAC7 and transcriptional activation of the orphan nuclear receptor NR4A1 while in cells with constitutive ROCK hyperactivity due to loss of function of the RhoGTPase activating protein Oligophrenin-1 (OPHN1), the orphan nuclear receptor NR4A1 is downregulated. Our study identify a new target of ROCK signaling via myosin phosphatase subunit (MYPT1) and Histone Deacetylase (HDAC7) at the nuclear level and provide new insights in the cellular functions of ROCK.

Keywords: Histone Deacetylase 7; Myosin phosphatase subunit 1; Oligophrenin 1; Orphan nuclear receptor NR4A1; Rho-kinase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus
Cells, Cultured
Cytoskeletal Proteins / genetics
Down-Regulation
GTPase-Activating Proteins / genetics
Histone Deacetylases / metabolism*
Humans
Induced Pluripotent Stem Cells / metabolism
Models, Biological
Mutation
Myosin-Light-Chain Phosphatase / metabolism
Nuclear Proteins / genetics
Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics*
Phosphorylation
Signal Transduction
Transcriptional Activation
rho-Associated Kinases / metabolism*

Substances

Cytoskeletal Proteins
GTPase-Activating Proteins
NR4A1 protein, human
Nuclear Proteins
Nuclear Receptor Subfamily 4, Group A, Member 1
OPHN1 protein, human
rho-Associated Kinases
Myosin-Light-Chain Phosphatase
PPP1R12A protein, human
HDAC7 protein, human
Histone Deacetylases