SFPQ associated with a co-activator for PPARγ, HELZ2, regulates key nuclear factors for adipocyte differentiation

SFPQ associated with a co-activator for PPARγ, HELZ2, regulates key nuclear factors for adipocyte differentiation
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DOI:
10.1016/j.bbrc.2021.05.014
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发表时间:
2021-05-27
影响因子:
3.1
通讯作者:
Yamada,Masanobu
Yamada,Masanobu
中科院分区:
生物学4区
文献类型:
--
作者:
Katano-Toki,Akiko;Yoshino,Satoshi;Yamada,Masanobu

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我们最近分离到一种新的过氧化物酶体增殖物激活受体γ的共激活剂--锌指解旋酶2(helicase with zinc finger 2,HELZ 2)。HELZ 2缺失小鼠对饮食诱导的肥胖和NAFFL/NASH具有抗性,并且HELZ 2在酪氨酸残基处被磷酸化。为了寻找与HELZ 2相关的因子,我们通过质谱分析与磷酸化HELZ 2共免疫沉淀的产物。我们鉴定了富含脯氨酸和谷氨酰胺(SFPQ)作为与酪氨酸磷酸化的HELZ 2相关的蛋白质。在3 T3-L1细胞中敲低SFPQ下调了转录因子的mRNA水平,包括Krox 20,Cebpβ和Cebp δ:早期脂肪细胞分化的关键因子。此外,敲低SFPQ抑制3 T3-L1细胞向成熟脂肪细胞的分化。这些发现表明,SFPQ与HELZ 2相关是脂肪细胞分化的重要的新的转录调控因子。
We recently isolated a novel co-activator of peroxisome proliferator-activated receptor γ, helicase with zinc finger 2 (HELZ2). HELZ2 null mice were resistant to diet-induced obesity and NAFFL/NASH, and HELZ2 was phosphorylated at tyrosine residues. In order to find a factor related to HELZ2, we analyzed products co-immunoprecipitated with phosphorylated HELZ2 by mass spectrometry analyses. We identified proline- and glutamine-rich (SFPQ) as a protein associating with tyrosine-phosphorylated HELZ2. The knockdown of SFPQ in 3T3-L1 cells downregulated mRNA levels of transcription factors includingKrox20,Cebpβ, andCebpδ: key factors for early-stage adipocyte differentiation. In addition, knockdown of SFPQ inhibited 3T3-L1 cell differentiation to mature adipocytes. These findings demonstrated that SFPQ associating with HELZ2 is an important novel transcriptional regulator of adipocyte differentiation.