当前位置：
X-MOL 学术
›
Chem. Sci.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
The anti-apoptotic proteins NAF-1 and iASPP interact to drive apoptosis in cancer cells†
Chemical Science ( IF 7.6 ) Pub Date : 2018-11-20 00:00:00 , DOI: 10.1039/c8sc03390k Anat Iosub-Amir 1, 2, 3, 4 , Fang Bai 5, 6, 7, 8, 9 , Yang-Sung Sohn 2, 3, 4, 10 , Luhua Song 9, 11, 12, 13 , Sagi Tamir 2, 3, 4, 10 , Henri-Baptiste Marjault 2, 3, 4, 10 , Guy Mayer 1, 2, 3, 4 , Ola Karmi 2, 3, 4, 10 , Patricia A. Jennings 9, 14, 15, 16 , Ron Mittler 17, 18, 19, 20, 21 , José N. Onuchic 5, 6, 7, 8, 9 , Assaf Friedler 1, 2, 3, 4 , Rachel Nechushtai 2, 3, 4, 10
Chemical Science ( IF 7.6 ) Pub Date : 2018-11-20 00:00:00 , DOI: 10.1039/c8sc03390k Anat Iosub-Amir 1, 2, 3, 4 , Fang Bai 5, 6, 7, 8, 9 , Yang-Sung Sohn 2, 3, 4, 10 , Luhua Song 9, 11, 12, 13 , Sagi Tamir 2, 3, 4, 10 , Henri-Baptiste Marjault 2, 3, 4, 10 , Guy Mayer 1, 2, 3, 4 , Ola Karmi 2, 3, 4, 10 , Patricia A. Jennings 9, 14, 15, 16 , Ron Mittler 17, 18, 19, 20, 21 , José N. Onuchic 5, 6, 7, 8, 9 , Assaf Friedler 1, 2, 3, 4 , Rachel Nechushtai 2, 3, 4, 10
Affiliation
|
Suppression of apoptosis is a key Hallmark of cancer cells, and reactivation of apoptosis is a major avenue for cancer therapy. We reveal an interaction between the two anti-apoptotic proteins iASPP and NAF-1, which are overexpressed in many types of cancer cells and tumors. iASPP is an inhibitory member of the ASPP protein family, whereas NAF-1 belongs to the NEET 2Fe–2S protein family. We show that the two proteins are stimulated to interact in cells during apoptosis. Using peptide array screening and computational methods we mapped the interaction interfaces of both proteins to residues 764–778 of iASPP that bind to a surface groove of NAF-1. A peptide corresponding to the iASPP 764–780 sequence stabilized the NAF-1 cluster, inhibited NAF-1 interaction with iASPP, and inhibited staurosporine-induced apoptosis activation in human breast cancer, as well as in PC-3 prostate cancer cells in which p53 is inactive. The iASPP 764–780 IC50 value for inhibition of cell death in breast cancer cells was 13 ± 1 μM. The level of cell death inhibition by iASPP 764–780 was altered in breast cancer cells expressing different levels and/or variants of NAF-1, indicating that the peptide activity is associated with NAF-1 function. We propose that the interaction between iASPP and NAF-1 is required for apoptosis activation in cancer cells. This interaction uncovers a new layer in the highly complex regulation of cell death in cancer cells and opens new avenues of exploration into the development of novel anticancer drugs that reactivate apoptosis in malignant tumors.
中文翻译：
抗凋亡蛋白NAF-1和iASPP相互作用以驱动癌细胞凋亡†
凋亡的抑制是癌细胞的关键特征，而凋亡的再激活是癌症治疗的主要途径。我们揭示了两种抗凋亡蛋白iASPP和NAF-1之间的相互作用，这两种蛋白在许多类型的癌细胞和肿瘤中均过表达。iASPP是ASPP蛋白家族的抑制成员，而NAF-1属于NEET 2Fe-2S蛋白家族。我们表明，这两种蛋白被刺激在细胞凋亡期间在细胞中相互作用。使用肽阵列筛选和计算方法，我们将两种蛋白质的相互作用界面映射到与NAF-1表面凹槽结合的iASPP残基764–778。与iASPP 764–780序列相对应的肽可稳定NAF-1簇，抑制NAF-1与iASPP的相互作用，并抑制星形孢菌素诱导的人乳腺癌细胞凋亡激活，以及p53失活的PC-3前列腺癌细胞中。iASPP 764–780 IC抑制乳腺癌细胞死亡的50值为13±1μM。在表达不同水平和/或NAF-1变体的乳腺癌细胞中，iASPP 764-780抑制细胞死亡的水平发生了变化，表明该肽的活性与NAF-1的功能有关。我们提出iASPP和NAF-1之间的相互作用是癌细胞中凋亡激活所必需的。这种相互作用揭示了癌细胞中高度复杂的细胞死亡调控中的新层，并为探索可重新激活恶性肿瘤细胞凋亡的新型抗癌药物的开发开辟了新的探索途径。
更新日期：2018-11-20
中文翻译：
抗凋亡蛋白NAF-1和iASPP相互作用以驱动癌细胞凋亡†
凋亡的抑制是癌细胞的关键特征，而凋亡的再激活是癌症治疗的主要途径。我们揭示了两种抗凋亡蛋白iASPP和NAF-1之间的相互作用，这两种蛋白在许多类型的癌细胞和肿瘤中均过表达。iASPP是ASPP蛋白家族的抑制成员，而NAF-1属于NEET 2Fe-2S蛋白家族。我们表明，这两种蛋白被刺激在细胞凋亡期间在细胞中相互作用。使用肽阵列筛选和计算方法，我们将两种蛋白质的相互作用界面映射到与NAF-1表面凹槽结合的iASPP残基764–778。与iASPP 764–780序列相对应的肽可稳定NAF-1簇，抑制NAF-1与iASPP的相互作用，并抑制星形孢菌素诱导的人乳腺癌细胞凋亡激活，以及p53失活的PC-3前列腺癌细胞中。iASPP 764–780 IC抑制乳腺癌细胞死亡的50值为13±1μM。在表达不同水平和/或NAF-1变体的乳腺癌细胞中，iASPP 764-780抑制细胞死亡的水平发生了变化，表明该肽的活性与NAF-1的功能有关。我们提出iASPP和NAF-1之间的相互作用是癌细胞中凋亡激活所必需的。这种相互作用揭示了癌细胞中高度复杂的细胞死亡调控中的新层，并为探索可重新激活恶性肿瘤细胞凋亡的新型抗癌药物的开发开辟了新的探索途径。
京公网安备 11010802027423号