Regulator of G-protein signaling 19 (RGS19) and its partner Gα-inhibiting activity polypeptide 3 (GNAI3) are required for zVAD-induced autophagy and cell death in L929 cells.
Regulator of G-protein signaling 19 (RGS19) and its partner Gα-inhibiting activity polypeptide 3 (GNAI3) are required for zVAD-induced autophagy and cell death in L929 cells.
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L929 细胞中 zVAD 诱导的自噬和细胞死亡需要 G 蛋白信号传导调节剂 19 (RGS19) 及其伴侣 G α 抑制活性多肽 3 (GNAI3)
DOI：
10.1371/journal.pone.0094634
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Han J
中科院分区：
文献类型：
--
作者：
Wu T;Li Y;Huang D;Han F;Zhang YY;Zhang DW;Han J
自噬具有多种生物学功能，参与多种生物学过程。由泛半胱天冬酶抑制剂苄氧基羰基-Val-Ala-Asp-（OMe）-氟甲基酮（zVAD）诱导的L929细胞死亡被证明是自噬介导的死亡，RIP 1和RIP 3都需要。还报道了zVAD可以诱导少量TNF产生，这被证明是zVAD诱导的L929细胞死亡所需的，这证明了自噬在zVAD诱导的L929细胞死亡中的贡献。为了研究RIP 3介导的细胞死亡，我们鉴定了G蛋白信号转导调节子19（RGS 19）作为RIP 3相互作用蛋白。我们发现RGS 19及其配偶体Gα抑制活性多肽3（GNAI 3）参与zVAD诱导的细胞死亡，但不参与TNF诱导的细胞死亡。RGS 19和GNAI 3在zVAD诱导的细胞死亡中的作用是它们参与zVAD诱导的自噬。通过使用小发夹RNA和化学抑制剂，我们进一步证明了zVAD诱导的自噬不仅需要RIP 1，RIP 3，PI 3 KC 3和Beclin-1，而且需要RGS 19和GNAI 3，并且这种自噬是zVAD诱导的TNF产生所需的。总的来说，我们的数据表明zVAD诱导的L929细胞死亡是自噬、半胱天冬酶抑制和TNF自分泌效应的协同结果。
Autophagy has diverse biological functions and is involved in many biological processes. The L929 cell death induced by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-(OMe)-fluoromethyl ketone (zVAD) was shown to be an autophagy-mediated death for which RIP1 and RIP3 were both required. It was also reported that zVAD can induce a small amount of TNF production, which was shown to be required for zVAD-induced L929 cell death, arguing for the contribution of autophagy in the zVAD-induced L929 cell death. In an effort to study RIP3 mediated cell death, we identified regulator of G-protein signaling 19 (RGS19) as a RIP3 interacting protein. We showed that RGS19 and its partner Gα-inhibiting activity polypeptide 3 (GNAI3) are involved in zVAD-, but not TNF-, induced cell death. The role of RGS19 and GNAI3 in zVAD-induced cell death is that they are involved in zVAD-induced autophagy. By the use of small hairpin RNAs and chemical inhibitors, we further demonstrated that zVAD-induced autophagy requires not only RIP1, RIP3, PI3KC3 and Beclin-1, but also RGS19 and GNAI3, and this autophagy is required for zVAD-induced TNF production. Collectively, our data suggest that zVAD-induced L929 cell death is a synergistic result of autophagy, caspase inhibition and autocrine effect of TNF.
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影响因子：
56.9
作者：
Zhang, Duan-Wu;Shao, Jing;Han, Jiahuai
通讯作者：
Han, Jiahuai
影响因子：
5.3
作者：
Nyfeler, Beat;Bergman, Philip;Murphy, Leon O.
通讯作者：
Murphy, Leon O.
DOI：
10.1126/stke.3582006pe44
发表时间：
2006-10-24
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
--
作者：
Vandenabeele, Peter;Vanden Berghe, Tom;Festjens, Nele
通讯作者：
Festjens, Nele
影响因子：
13.3
作者：
Wu, You-Tong;Tan, Hui-Ling;Shen, Han-Ming
通讯作者：
Shen, Han-Ming
影响因子：
56.9
作者：
Yu, L;Alva, A;Lenardo, MJ
通讯作者：
Lenardo, MJ