Feb 15, 2021 · Nuclear histone deacetylase 4 (HDAC4) represses MEF2-mediated transcription, implicated in the development of heart failure. CaMKII-dependent phosphorylation drives nucleus-to-cytoplasm HDAC4 shuttling, but protein kinase A (PKA) is also linked to HDAC4 translocation.

HDAC4 is the most well-characterized member of the class IIa family in terms of the number of identified PTMs, which include phosphorylation, acetylation, sumoylation, and disulfide bond formation (Fig. 1A). Furthermore, many of the enzymes regulating these …

May 5, 2012 · In this study, we report that endogenous HDAC4 and HDAC5 in VSM are activated in a Ca 2+ - and CaMKIIδ2-dependent manner. We further show that AngII-and PDGF-dependent phosphorylation of HDAC4 and HDAC5 is reduced when CaMKIIδ2 expression is suppressed or CaMKIIδ2 activity is attenuated.

Collectively, CaMKII limits nuclear localization of HDAC4, while PKA favors HDAC4 nuclear retention and S265/266 is essential for PKA-mediated regulation. These pathways thus compete in HDAC4 nuclear localization and transcriptional regulation in cardiac signaling.

HDAC4, -5, -7, and -9 possess a definitive bipartite structure (31). The C terminus contains a conserved deacetylase do-main and a hydrophobic nuclear export sequence (NES), which promotes cytoplasmic accumulation (32) (Fig. 1).

HDAC4, a class Ⅱ HDAC, colocalizes with α-synuclein and ubiquitin in Lewy bodies and also accumulates in the nuclei of dopaminergic neurons in PD models.

HDAC4 phosphorylation enhances EC motility in wound healing assays and facilitates EC tube formation. In the research of tasquinimod, an orally active anti-angiogenic drug, John Isaacs et al. considered HDAC4 as the target of its anti-angiogenic activity.

Nov 23, 2020 · The alpha subunit of the heterotrimeric G protein complex (Gαi2) also suppresses HDAC4 via an indirect mechanism involving the protein kinase C (PKC) signaling . Importantly, HDAC4 is a direct target of several miRNAs with myogenic function, such as miR-1/206 and miRNAs of the mir-29 family (49, 72, 73). This generates further regulatory loops ...

Feb 15, 2021 · Nuclear histone deacetylase 4 (HDAC4) represses MEF2-mediated transcription, implicated in the development of heart failure. CaMKII-dependent phosphorylation drives nucleus-to-cytoplasm HDAC4 shuttling, but protein kinase A (PKA) is also linked to HDAC4 translocation.

Aug 1, 2014 · We demonstrate that PKA-dependent phosphorylated HDAC4 is released from Runx2 bound to the MMP-13 promoter in these cells. Point mutation of Ser-740 in rHDAC4 prevents the release of HDAC4 from Runx2 on the MMP-13 promoter and also prevents the PTH stimulation of MMP-13 transcription.