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截短型 Livin 的过表达揭示了与 caspase-3 的复杂相互作用。

Overexpression of the truncated form of Livin reveals a complex interaction with caspase-3.

机构信息

Division of Thoracic Cancer, West China Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, P.R. China.

出版信息

Int J Oncol. 2013 Jun;42(6):2037-45. doi: 10.3892/ijo.2013.1883. Epub 2013 Apr 4.

DOI:10.3892/ijo.2013.1883
PMID:23563149
Abstract

Disruption in apoptosis are involved in cancer development and progression. Livin-β, has been identified as a critical modulator for cell death in several tumor cell lines. It was demonstrated that a truncated fragment of Livin-β (tLivin) without its N-terminal 52 amino acids is produced in cells through protein cleavage. However, the biological consequence of the cleavage remains largely ignored. In the present study, we report that tLivin exerted a pro-apoptotic effect on cells. The subcellular localization of tLivin was mainly restricted to the cytoplasm. To explore the underlying mechanism, we observed an elevated caspase-3 activity which may account for the apoptosis. Furthermore, we observed that tLivin was further cleaved into a smaller fragment in cells. This second cleavage was possibly related to activated caspase-3. The resulted C-terminal fragment (livC) was an anti-apoptotic factor. Our study may help to deepen our understanding of the role of Livin in the regulation of cell death.

摘要

凋亡失调参与癌症的发生和发展。Livin-β已被确定为几种肿瘤细胞系中细胞死亡的关键调节剂。研究表明,Livin-β的截短片段(tLivin)通过蛋白切割在细胞中产生,没有其 N 端的 52 个氨基酸。然而,切割的生物学后果在很大程度上仍被忽视。在本研究中,我们报告 tLivin 对细胞具有促凋亡作用。tLivin 的亚细胞定位主要局限于细胞质。为了探索潜在的机制,我们观察到 caspase-3 活性升高,这可能是细胞凋亡的原因。此外,我们观察到 tLivin 在细胞中进一步切割成较小的片段。这种第二次切割可能与激活的 caspase-3 有关。所得的 C 端片段(livC)是一种抗凋亡因子。我们的研究可能有助于加深我们对 Livin 在细胞死亡调控中的作用的理解。

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1
Overexpression of the truncated form of Livin reveals a complex interaction with caspase-3.截短型 Livin 的过表达揭示了与 caspase-3 的复杂相互作用。
Int J Oncol. 2013 Jun;42(6):2037-45. doi: 10.3892/ijo.2013.1883. Epub 2013 Apr 4.
2
Subcellular localization determines the delicate balance between the anti- and pro-apoptotic activity of Livin.亚细胞定位决定了生存素抗凋亡与促凋亡活性之间的微妙平衡。
Apoptosis. 2007 Jul;12(7):1129-42. doi: 10.1007/s10495-006-0049-1.
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Expression and role of the inhibitor of apoptosis protein livin in chemotherapy sensitivity of ovarian carcinoma.凋亡抑制蛋白 livin 在卵巢癌化疗敏感性中的表达及作用。
Int J Oncol. 2012 Sep;41(3):1021-8. doi: 10.3892/ijo.2012.1540. Epub 2012 Jul 3.
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Expression of livin in gastric cancer and induction of apoptosis in SGC-7901 cells by shRNA-mediated silencing of livin gene.livin 在胃癌中的表达及 RNA 干扰 livin 基因对 SGC-7901 细胞凋亡的诱导作用
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Cyclic GMP/protein kinase G type-Iα (PKG-Iα) signaling pathway promotes CREB phosphorylation and maintains higher c-IAP1, livin, survivin, and Mcl-1 expression and the inhibition of PKG-Iα kinase activity synergizes with cisplatin in non-small cell lung cancer cells.环鸟苷酸/蛋白激酶 G 型-Iα (PKG-Iα) 信号通路促进 CREB 磷酸化,维持较高的 c-IAP1、livin、survivin 和 Mcl-1 的表达,PKG-Iα 激酶活性的抑制与顺铂在非小细胞肺癌细胞中具有协同作用。
J Cell Biochem. 2012 Nov;113(11):3587-98. doi: 10.1002/jcb.24237.
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[Expression of livin in gastric cancer and effect of silencing of the livin gene on apoptosis in gastric cancer cells].[Livin在胃癌中的表达及Livin基因沉默对胃癌细胞凋亡的影响]
Zhonghua Zhong Liu Za Zhi. 2007 Aug;29(8):570-4.
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Proteolytic cleavage of Livin (ML-IAP) in apoptotic melanoma cells potentially mediated by a non-canonical caspase.凋亡黑素瘤细胞中Livin(ML-IAP)的蛋白水解切割可能由一种非典型半胱天冬酶介导。
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Livin may serve as a marker for prognosis of bladder cancer relapse and a target of bladder cancer treatment.Livin可能作为膀胱癌复发预后的标志物以及膀胱癌治疗的靶点。
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Knockdown of Livin inhibits growth and invasion of gastric cancer cells through blockade of the MAPK pathway in vitro and in vivo.敲低 Livin 可通过阻断 MAPK 通路抑制胃癌细胞的生长和侵袭,无论是在体外还是体内。
Int J Oncol. 2014 Jan;44(1):276-84. doi: 10.3892/ijo.2013.2171. Epub 2013 Nov 12.
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The inhibitor of apoptosis protein Livin (ML-IAP) plays a dual role in tumorigenicity.凋亡抑制蛋白Livin(ML-IAP)在肿瘤发生过程中发挥双重作用。
Cancer Res. 2009 Jul 1;69(13):5475-80. doi: 10.1158/0008-5472.CAN-09-0424. Epub 2009 Jun 23.

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Transl Cancer Res. 2020 May;9(5):3426-3434. doi: 10.21037/tcr-19-1979.
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Expression of Livin and PlGF in human osteosarcoma is associated with tumor progression and clinical outcome.Livin和胎盘生长因子(PlGF)在人骨肉瘤中的表达与肿瘤进展及临床预后相关。
Oncol Lett. 2018 Oct;16(4):4953-4960. doi: 10.3892/ol.2018.9239. Epub 2018 Jul 31.
3
tLivin displays flexibility by promoting alternative cell death mechanisms.
tLivin通过促进替代性细胞死亡机制表现出灵活性。
PLoS One. 2014 Jun 24;9(6):e101075. doi: 10.1371/journal.pone.0101075. eCollection 2014.