Faculty Opinions recommendation of AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability.

Author(s):  
Bruce Kemp
2020 ◽  
Vol 10 (11) ◽  
pp. 1836-1845
Author(s):  
Tao Jiang ◽  
Qingzhen Chen ◽  
Min Shao ◽  
Zhen Shen ◽  
Gang Wang ◽  
...  

Activation of Protein Kinase AMP-Activated Catalytic Subunit Alpha (AMPKα) is an important regulatory pathway for osteogenic differentiation. STAT4 acts as a transcriptional activity factor to regulate the transcription of many genes and is potentially a regulatory factor for AMPKα transcription activity. To confirm the regulatory effect of STAT4 on AMPKα and the effect of STAT4 on osteogenic differentiation, the promoter sequence of AMPKα was analyzed via bioinformatics, the STAT4 overexpression vector was constructed and transfected into human osteoblast-like cells MG-63 by cationic liposome, fluorescence quantitative PCR (RT-qPCR) and western blotting technologies were used to detect the effect of STAT4 on the expression of AMPKα. MTT and ALP activity assays were also used to verify the effect of STAT4 on the proliferation and maturation of osteoblasts by regulating AMPKα expression. Our results showed that STAT4 was a co-transcriptional regulator of AMPKα1 and AMPKα2, which combined the enrichment region of CpG on the promoter sequence of AMPKα1/2. Overexpression of STAT4 significantly increased the expression of AMPKα1 and AMPKα2, which promoted the proliferation and maturation of osteoblasts. We concluded that STAT4 was a transcriptional activator of AMPKα and promoting STAT4 expression enhances the proliferation and differentiation activity of AMPKα in osteoblasts.


Author(s):  
Takahiro Ikeda ◽  
Shun Watanabe ◽  
Takakazu Mitani

Abstract Genistein exerts anti-adipogenic effects, but its target molecules remain unclear. Here, we delineated the molecular mechanism underlying the anti-adipogenic effect of genistein. A pulldown assay using genistein-immobilized beads identified adenine nucleotide translocase-2 as a genistein-binding protein in adipocytes. Adenine nucleotide translocase-2 exchanges ADP/ATP through the mitochondrial inner membrane. Similar to the knockdown of adenine nucleotide translocase-2, genistein treatment decreased ADP uptake into the mitochondria and ATP synthesis. Genistein treatment and adenine nucleotide translocase-2 knockdown suppressed adipogenesis and increased phosphorylation of AMP-activated protein kinase. Adenine nucleotide translocase-2 knockdown reduced the transcriptional activity of CCAAT/enhancer-binding protein β, whereas AMP-activated protein kinase inhibition restored the suppression of adipogenesis by adenine nucleotide translocase-2 knockdown. These results indicate that genistein interacts directly with adenine nucleotide translocase-2 to suppress its function. The downregulation of adenine nucleotide translocase-2 reduces the transcriptional activity of CCAAT/enhancer-binding protein β via activation of AMP-activated protein kinase, which consequently represses adipogenesis.


2004 ◽  
Vol 44 (Supplement 1) ◽  
pp. S435-S438 ◽  
Author(s):  
Yoshihiko Kakinuma ◽  
Yanan Zhang ◽  
Motonori Ando ◽  
Tetsuro Sugiura ◽  
Takayuki Sato

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