Positioning atypical protein kinase C isoforms in the UV-induced apoptotic signaling cascade
Positioning atypical protein kinase C isoforms in the UV-induced apoptotic signaling cascade
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DOI：
10.1128/mcb.17.8.4346
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发表时间：
1997-08-01
影响因子：
5.3
通讯作者：
Moscat, J
中科院分区：
文献类型：
--
作者：
Berra, E;Municio, MM;Moscat, J
最近的研究证明，非典型蛋白激酶C(APKC)亚型参与了重要的细胞功能，如细胞增殖和生存。将细胞暴露在可诱导细胞凋亡的遗传毒性刺激下，如紫外线照射，可导致体内非典型PKC活性的严重抑制。在这项研究中，我们讨论了这一现象与参与细胞凋亡反应的不同蛋白质之间的关系。我们发现：(I)aPKC活性的抑制先于紫外线诱导的细胞凋亡；(Ii)紫外线诱导的aPKC抑制和凋亡不依赖于P53；(Iii)bcl2蛋白是aPKC活性的有效调节者；以及(Iv)aPKC位于白细胞介素类酶系统的上游，这是PAR-4(一种选择性的aPKC抑制剂)和紫外线诱导细胞凋亡所必需的。我们还证明，抑制aPKC活性会导致丝裂原活化蛋白(MAP)激酶活性降低，同时p38活性增加。这两种效应在诱导PAR-4表达和紫外线照射所致的细胞凋亡中起着关键作用。综上所述，这些结果阐明了APKCs在紫外线诱导的凋亡途径中的位置，并强烈表明MAP激酶在这一信号级联中发挥作用。
Recent studies have documented the involvement of the atypical protein kinase C (aPKC) isoforms in important cellular functions such as cell proliferation and survival. Exposure of cells to a genotoxic stimulus that induces apoptosis, such as UV irradiation, leads to a profound inhibition of the atypical PKC activity in vivo. In this study, we addressed the relationship between this phenomenon and different proteins involved in the apoptotic response. We show that (i) the inhibition of the aPKC activity precedes UV-induced apoptosis; (ii) UV-induced aPKC inhibition and apoptosis are independent of p53; (iii) Bcl-2 proteins are potent modulators of aPKC activity; and (iv) the aPKCs are located upstream of the interleukin-converting enzymelike protease system, which is required for the induction of apoptosis by both Par-4 (a selective aPKC inhibitor) and UV irradiation. We also demonstrate here that inhibition of aPKC activity leads to a decrease in mitogen-activated protein (MAP) kinase activity and simultaneously an increase in p38 activity. Both effects are critical for the induction of apoptosis in response to Par-4 expression and UV irradiation. Collectively, these results clarify the position of the aPKCs in the UV-induced apoptotic pathway and strongly suggest that MAP kinases play a role in this signaling cascade.