Normal p53 function in primary cells deficient for Siah genes
Normal p53 function in primary cells deficient for Siah genes
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DOI：
10.1128/mcb.22.23.8155-8164.2002
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发表时间：
2002-12-01
影响因子：
5.3
通讯作者：
Bowtell, DDL
中科院分区：
文献类型：
--
作者：
Frew, IJ;Dickins, RA;Bowtell, DDL
过表达研究表明，Siah1蛋白可能作为p53介导的细胞反应的效应器和有丝分裂进程的调节剂。我们已经使用Siah基因敲除小鼠测试了这些假设。Siah1a和Siah1b不诱导内源性p53在组织，原代小鼠胚胎成纤维细胞（MEFs）或胸腺细胞的激活。此外，缺乏Siah1a、Siah1b、Siah2或Siah2和Siah1a的原代MEFs显示正常的细胞周期进展、增殖、p53介导的衰老和G期细胞周期停滞。缺乏Siah1a、Siah2或Siah2和Siah1a的原代胸腺细胞，缺乏Siah1a、Siah1b或Siah2的E1A转化的MEFs，以及Siah1b缺失的ES细胞都经历了正常的p53介导的凋亡。最后，抑制Siah1b表达Siah2 Siah1a双突变细胞未能抑制细胞分裂，p53介导的诱导p21表达，或细胞周期停滞。我们的功能丧失实验不支持Siah基因在p53介导的反应或有丝分裂中的一般作用。
Overexpression studies have suggested that Siah1 proteins may act as effectors of p53-mediated cellular responses and as regulators of mitotic progression. We have tested these hypotheses using Siah gene knockout mice. Siah1a and Siah1b were not induced by activation of endogenous p53 in tissues, primary murine embryonic fibroblasts (MEFs) or thymocytes. Furthermore, primary MEFs lacking Siah1a, Siah1b, Siah2, or both Siah2 and Siah1a displayed normal cell cycle progression, proliferation, p53-mediated senescence, and G, phase cell cycle arrest. Primary thymocytes deficient for Siah1a, Siah2, or both Siah2 and Siah1a, E1A-transformed MEFs lacking Siah1a, Siah1b, or Siah2, and Siah1b-null ES cells all underwent normal p53-mediated apoptosis. Finally, inhibition of Siah1b expression in Siah2 Siah1a double-mutant cells failed to inhibit cell division, p53-mediated induction of p21 expression, or cell cycle arrest. Our loss-of-function experiments do not support a general role for Siah genes in p53-mediated responses or mitosis.