Cell cycle regulation via p53 phosphorylation by a 5′-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, in a human hepatocellular carcinoma cell line

Cell cycle regulation via p53 phosphorylation by a 5′-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, in a human hepatocellular carcinoma cell line
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DOI:
10.1006/bbrc.2001.5627
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发表时间:
2001-09-21
影响因子:
3.1
通讯作者:
Esumi, H
Esumi, H
中科院分区:
生物学4区
文献类型:
--
作者:
Imamura, K;Ogura, T;Esumi, H

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5 - 氨基咪唑 - 4 - 甲酰胺 - 1 - β - D - 呋喃核糖苷(AICAR)是腺苷酸活化蛋白激酶(AMPK)的激活剂以及嘌呤从头合成的调节剂。先前有一些报道表明,AICAR处理通过调节AMPK或嘌呤从头合成来抑制细胞生长。我们发现,在HepG2细胞中,由于p53积累(与p53 - Ser15磷酸化相关),AICAR处理可抑制细胞生长。此外,在p53 - Ser15周围发现了一个与AMPK磷酸化的共有基序非常相似的基序,并且在AICAR处理的HepG2细胞中检测到Ser15磷酸化,就像AMPK在体外进行磷酸化一样。我们的研究结果表明,AICAR可能通过p53磷酸化来调节细胞生长,同时也表明了p53磷酸化的可能性。(C)2001学术出版社
5-Aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) is an activator of AMP activated protein kinase (AMPK) and a regulator of de novo purine synthesis. There are several earlier reports indicating that AICAR treatment suppresses cell growth via regulation of AMPK or de novo purine synthesis. We found cell growth to be suppressed by AICAR treatment in HepG2 because of p53 accumulation, which was associated with p53-Ser15 phosphorylation. Moreover, a motif very similar to the consensus motif of AMPK phosphorylation was found around p53-Ser15, and Ser15 phosphorylation was detected in AICAR treated HepG2 as was in vitro phosphorylation by AMPK. Our results suggest that AICAR may regulate cell growth via p53 phosphorylation, and also indicate the possibility of p53 phosphorylation. (C) 2001 Academic Press.