SIRT7 Deacetylates STRAP to Regulate p53 Activity and Stability
SIRT7 Deacetylates STRAP to Regulate p53 Activity and Stability
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SIRT7 使 STRAP 去乙酰化以调节 p53 活性和稳定性
DOI：
10.3390/ijms21114122
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发表时间：
2020
影响因子：
5.6
通讯作者：
Luo Jianyuan
中科院分区：
文献类型：
--
作者：
Yu Miao;Shi Xiaoyan;Ren Mengmeng;Liu Lu;Qi Hao;Zhang Chi;Zou Junhua;Qiu Xiaoyan;Zhu Wei-Guo;Zhang Ying E.;Wang Wengong;Luo Jianyuan
丝氨酸-苏氨酸激酶受体相关蛋白（SRAP）作为TGF-β和p53信号传导的调节剂起作用，其参与响应于各种应激的细胞增殖和细胞死亡的调节。在这里，我们证明了STRAP乙酰化在p53介导的细胞周期阻滞和凋亡中起着重要作用。STRAP在赖氨酸147、148和156处被乙酰转移酶CREB结合蛋白（CBP）乙酰化，并且乙酰化被脱乙酰酶sirtuin 7（SIRT 7）逆转。STRAP在赖氨酸147、148和156（3 KR或3 KQ）处的低乙酰化或高乙酰化突变影响其p53的活化和稳定。此外，在5-氟尿嘧啶（5-FU）处理后，STRAP从细胞质移动到细胞核并促进STRAP乙酰化。我们发现STRAP的调节将p53与影响p53活性和稳定性的SIRT 7联系起来。
Serine-threonine kinase receptor-associated protein (STRAP) functions as a regulator of both TGF-β and p53 signaling that participates in the regulation of cell proliferation and cell death in response to various stresses. Here, we demonstrate that STRAP acetylation plays an important role in p53-mediated cell cycle arrest and apoptosis. STRAP is acetylated at lysines 147, 148, and 156 by the acetyltransferases CREB-binding protein (CBP) and that the acetylation is reversed by the deacetylase sirtuin7 (SIRT7). Hypo- or hyperacetylation mutations of STRAP at lysines 147, 148, and 156 (3KR or 3KQ) influence its activation and stabilization of p53. Moreover, following 5-fluorouracil (5-FU) treatment, STRAP is mobilized from the cytoplasm to the nucleus and promotes STRAP acetylation. Our finding on the regulation of STRAP links p53 with SIRT7 influencing p53 activity and stability.