Departmento de Biología Celular, Fisiología e Immunología, Facultad de Medicina, Universidad de Córdoba, Avda. Menéndez Pidal, s/n, E-14004 Córdoba, Spain.
Biol Chem. 2009 Oct;390(10):1079-83. doi: 10.1515/BC.2009.112.
The different activities of the tumor suppressor p53 are tightly regulated by various negative and positive feedback loops, which allow accurate control of its function. Here we show that the p53-inducible ubiquitin E3 ligase Siah-1L can bind to the p53 phosphorylating kinase HIPK2 and thus allows its ubiquitination and proteasomal elimination. Siah-1L also eliminates the HIPK family member HIPK3, indicating that its activity is not restricted to one member of the HIPK family. The stimulating effect of HIPK2 on p53-triggered transcription is counteracted by Siah-1L, thus showing the occurrence of another negative feedback loop controlling the p53 response.
肿瘤抑制因子 p53 的不同活性受到各种负反馈和正反馈环的严格调控，这些调控环允许对其功能进行精确控制。在这里，我们表明 p53 诱导的泛素 E3 连接酶 Siah-1L 可以与 p53 磷酸化激酶 HIPK2 结合，从而允许其泛素化和蛋白酶体消除。Siah-1L 还消除了 HIPK 家族成员 HIPK3，表明其活性不仅限于 HIPK 家族的一个成员。HIPK2 对 p53 触发的转录的刺激作用被 Siah-1L 抵消，从而显示出另一个负反馈环的发生，该负反馈环控制 p53 反应。
