HSF1 依赖性转录激活
中文名称
通路描述
HSF1 获得 DNA 结合活性对于转录激活是必要的但不充分。除了具有序列特异性 DNA 结合域外，HSF1 还包含一个 C 端区域，参与目标基因的转录激活。然而，转录激活域本身的转录激活能力不受应激敏感。相反，它受 HSF1 的调节域控制（氨基酸 221-310），在正常生理条件下抑制转录激活能力。HSF1 转录激活域可分为两个不同的区域：激活域 1（AD1）和激活域 2（AD2）。AD1 和 AD2 各自包含对于转录起始和延伸都重要的残基。AD1 和 AD2 中酸性残基的突变优先影响 HSF1 刺激转录起始的能力，而苯丙氨酸残基的突变优先影响延伸的激活。DNA 结合但转录不活跃的 HSF1 的激活被认为是在多种丝氨酸残基诱导的 HSF1 磷酸化后发生的（Ding XZ et al. 1997; Holmberg CI et al. 2001; Guettouche T et al. 2005）。在暴露于热的细胞中，观察到获得 HSE DNA 结合活性先于 HSF1 的磷酸化。虽然有足够的证据表明 HSF1 的磷酸化对于调节 HSF1 转录激活能力是必要的，但应激刺激和参与其中的激酶/磷酸酶机制尚未明确。
英文描述
HSF1-dependent transactivation Acquisition of DNA binding activity by HSF1 is necessary but insufficient for transcriptional activation (Cotto JJ et al. 1996; Trinklein ND et al. 2004). In addition to having a sequence-specific DNA binding domain, HSF1 contains a C-terminal region which is involved in activating the transcription of the target genes (Green M et al. 1995). However, the transactivating ability of the transactivation domain itself is not stress sensitive. Rather, it's controled by a regulatory domain of HSF1 (amino acids 221-310), which represses the transactivating ability under normal physiological conditions (Green M et al. 1995; Zuo J et al. 1995; Newton EM et al. 1996). The HSF1 transactivation domain can be divided into two distinct regions, activation domain 1 (AD1) and activation domain 2 (AD2) (Brown SA et al. 1998). AD1 and AD2 each contain residues that are important for both transcriptional initiation and elongation. Mutations in acidic residues in both AD1 and AD2 preferentially affect the ability of HSF1 to stimulate transcriptional initiation, while mutations in phenylalanine residues preferentially affect stimulation of elongation (Brown SA et al. 1998). Activation of the DNA-bound but transcriptionally incompetent HSF1 is thought to occur upon stress induced HSF1 phosphorylation at several serine residues (Ding XZ et al. 1997; Holmberg CI et al. 2001; Guettouche T et al. 2005). In cells exposed to heat, acquisition of HSE DNA-binding activity was observed to precede phosphorylation of HSF1 (Cotto JJ et al. 1996; Kline MP & Morimoto RI 1997). While there is a sufficient evidence to suggest that phosphorylation of HSF1 is essential to modulate HSF1 transactiviting capacity, mechanisms behind stress stimuli and kinases/phosphatases involved have not been clearly established.
所含基因
18 个基因