Fine Tuning of Protein Kinase C (PKC) Isoforms in Cancer: Shortening the Distance from the Laboratory to the Bedside.

Bosco R; Melloni E; Celeghini C; Rimondi E; Vaccarezza M; Zauli G

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Fine Tuning of Protein Kinase C (PKC) Isoforms in Cancer: Shortening the Distance from the Laboratory to the Bedside.

机译：癌症中蛋白激酶C（PKC）亚型的微调：缩短从实验室到床边的距离。

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The serine/threonine protein kinase C (PKC) family was first identified as intracellular receptor(s) for the tumor promoting agents phorbol esters. Thirty years after the discovery of PKC, the role of specific PKC isoforms has been described in relationship with an altered pattern of expression in different types of cancer and a good number of small molecule inhibitors (inhibitory peptides, antisense oligonucleotides or natural compounds) targeting PKC are now available. Despite all these achievements and a huge amount of basic research studies on the biochemical regulation of PKC, there has been a delay in clinical trials with drugs targeting PKC function. This delay is easily explained taking into account the extreme biological complexity of the PKC family of isoforms and the incomplete understanding of the specific role of each PKC isozyme in different types of cancers. Some of the difficulties in developing pharmacological compounds selectively tuning the different PKCs have started to be overcome. In this review, the growing evidences of the role of the PKC isoforms alpha, betaII, delta, epsilon, zeta and iota is in promoting or counteracting tumor progression will be discussed in relationship with promising therapeutic perspectives.

机译：丝氨酸/苏氨酸蛋白激酶C（PKC）家族首先被确定为肿瘤促进剂佛波酯的细胞内受体。发现PKC后三十年，已描述了特定PKC同工型的作用与不同类型癌症中表达模式的改变以及大量靶向PKC的小分子抑制剂（抑制性肽，反义寡核苷酸或天然化合物）有关现在可用。尽管取得了所有这些成就并进行了大量有关PKC生化调节的基础研究，但针对PKC功能的药物的临床试验仍存在延迟。考虑到PKC同工型家族的极端生物学复杂性以及对每种PKC同工酶在不同类型的癌症中的特定作用的不完全了解，可以很容易地解释这种延迟。在开发选择性调节不同PKC的药理化合物方面的一些困难已开始克服。在这篇综述中，将结合有前途的治疗观点讨论PKC同工型α，βII，δ，ε，ζ和iota在促进或抵抗肿瘤进展中作用的越来越多的证据。

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《Mini reviews in medicinal chemistry》 |2011年第3期|共15页
作者
Bosco R; Melloni E; Celeghini C; Rimondi E; Vaccarezza M; Zauli G;
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1. Fine Tuning of Protein Kinase C (PKC) Isoforms in Cancer: Shortening the Distance from the Laboratory to the Bedside. [J] . Bosco R, Melloni E, Celeghini C, Mini reviews in medicinal chemistry . 2011,第3期

机译：癌症中蛋白激酶C（PKC）亚型的微调：缩短从实验室到床边的距离。
2. Protein kinase C isoforms in normal and chronic myeloid leukemic neutrophils. Distinct signal for PKC alpha by immunodetection on PVDF membrane, decreased expression of PKC alpha and increased expression of PKC delta in leukemic neutrophils. [J] . Balasubramanian N, Advani SH, Zingde SM Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis . 1998,第7期

机译：正常和慢性粒细胞白血病中性粒细胞中的蛋白激酶C亚型。通过免疫检测PVDF膜上的PKCα的信号不同，白血病中性粒细胞中PKCα的表达降低和PKCδ的表达增加。
3. Protein kinase C (PKC) isoforms in cancer, tumor promotion and tumor suppression [J] . Isakov Noah Seminars in cancer biology . 2018,第期

机译：蛋白激酶C（PKC）同种型癌症，肿瘤促进和肿瘤抑制
4. Protein Kinase C Isoform (PKC) Peptide Activator/Inhibitors Exert Cardioprotective Effects in Polymorphonuclear Leukocyte (PMN)-induced Ischemia/Reperfusion (I/R) Injury [C] . Lindon H. Young, Aisha Phillipson, Didi Omiyi American Peptide Symposium . 2006

机译：蛋白激酶C同种型（PKC）肽活化剂/抑制剂在多核白细胞（PMN）中施加心脏保护作用 - 诱导的缺血/再灌注（I / R）损伤
5. Using integrins to fine tune CD4+ T cell responses: How the integrin regulatory proteins calpain, PIPKIgamma'90, talin and focal adhesion kinase work together to regulate CD4+ T cell activation. [D] . Wernimont, Sarah A. 2011

机译：使用整合素来微调CD4 + T细胞反应：整合素调节蛋白calpain，PIPKIgamma'90，talin和黏着斑激酶如何协同作用来调节CD4 + T细胞活化。
6. Protein Kinase C (PKC)ζ Pseudosubstrate Inhibitor Peptide Promiscuously Binds PKC Family Isoforms and Disrupts Conventional PKC Targeting and Translocation [O] . Amy S. Bogard, Steven J. Tavalin -1

机译：蛋白激酶C（PKC）ζ伪底物抑制剂肽与PKC家族亚型混杂结合并破坏常规PKC的靶向和转运
7. Protein Kinase C (PKC)ζ Pseudosubstrate Inhibitor Peptide Promiscuously Binds PKC Family Isoforms and Disrupts Conventional PKC Targeting and Translocation [O] . Amy S. Bogard, Steven J. Tavalin 2015

机译：蛋白质激酶C（PKC）ζ假抑制抑制剂肽混合结合PKC系列同种型并破坏常规PKC靶向和易位

Fine Tuning of Protein Kinase C (PKC) Isoforms in Cancer: Shortening the Distance from the Laboratory to the Bedside.

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