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The tubulin deacetylase sirtuin-2 regulates neuronal differentiation through the ERK/CREB signaling pathway.

Abstract：

:Modification of microtubule (MT) dynamics is important for diverse aspects of cellular function including differentiation, cargo trafficking, migration, and adhesion. MTs also play a crucial role in the progression of neuronal development. The MT deacetylase Sirtuin 2 (Sirt2) and histone deacetylase 6 (HDAC6) regulate MT dynamics by deacetylating alpha-tubulin (α-tubulin). In this study, we investigated the role of MT deacetylation in the progression of neuronal differentiation. For this, we examined acetylated α-tubulin levels during the differentiation of stem cells into neurons. Acetylated α-tubulin levels were significantly altered during differentiation, and these changes were abolished following treatment with 10 μM AGK2 (Sirt2 inhibitor) or 3 μM tubastatin A (HDAC6 inhibitor). However, neural-specific protein expression (Nestin, NF-M, and MAP-2) was reduced in AGK2-treated hBM-MSCs (AGK-MSCs), but not in tubastatin A-treated hBM-MSCs (Tubastatin A-MSCs). Inhibition of Sirt2 led to a decrease in ERK phosphorylation (p-ERK) level, but HDAC6 inhibition had no such effect. Similar results were obtained for CREB phosphorylation (p-CREB). The results suggest that Sirt2 plays a crucial role in neuronal differentiation via the ERK-CREB signaling pathway.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Jeong SG,Cho GW

doi

10.1016/j.bbrc.2016.11.031

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

182-187

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)31887-3

journal_volume

482

pub_type

杂志文章

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