Less understood issues: p21(Cip1) in mitosis and its therapeutic potential

Kreis N-N; Louwen F.; Yuan J.

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Less understood issues: p21(Cip1) in mitosis and its therapeutic potential

机译：鲜为人知的问题：有丝分裂中的p21（Cip1）及其治疗潜力

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p21(Cip1) is a multifunctional protein and a key player in regulating different cellular processes. The transcription of p21 is regulated by p53-dependent and -independent pathways. The expression of p21 is increased in response to various cellular stresses to arrest the cell cycle and ensure genomic stability. p21 has been shown to be a tumor suppressor and an oncogene as well. The function of p21 in mitosis has been proposed but not systematically studied. We have recently shown that p21 binds to and inhibits the activity of Cdk1/cyclin B1, and is important for a fine-tuned mitotic progression. Loss of p21 prolongs the duration of mitosis and results in severe mitotic defects like chromosome segregation and cytokinesis failures promoting consequently genomic instability. Moreover, p21 is dramatically stabilized in mitotic tumor cells upon treatment with mitotic agents like paclitaxel or mitotic kinase inhibitors. Increased p21 is mainly localized in the cytoplasm and associates with cell survival indicating a crucial role of p21 in susceptibility to mitotic agents in tumor cells. In this review we will briefly summarize the structure and general physiological functions as well as regulation of p21, discuss in detail its role in mitosis and its potential to serve as a therapeutic target.

机译：p21（Cip1）是一种多功能蛋白，是调节不同细胞过程的关键参与者。p21 的转录受 p53 依赖性和不依赖性途径的调节。p21的表达在各种细胞应激下增加，以阻止细胞周期并确保基因组稳定性。p21 已被证明是肿瘤抑制因子和致癌基因。p21在有丝分裂中的功能已被提出，但尚未系统研究。我们最近表明，p21 结合并抑制 Cdk1/细胞周期蛋白 B1 的活性，并且对微调的有丝分裂进程很重要。p21 的缺失会延长有丝分裂的持续时间，并导致严重的有丝分裂缺陷，如染色体分离和胞质分裂失败，从而促进基因组不稳定性。此外，p21 在用有丝分裂药物（如紫杉醇或有丝分裂激酶抑制剂）治疗后在有丝分裂肿瘤细胞中显着稳定。p21 的增加主要位于细胞质中，并与细胞存活相关，表明 p21 在肿瘤细胞对有丝分裂剂的易感性中起着至关重要的作用。本文将简要总结p21的结构和一般生理功能以及调控，详细讨论p21在有丝分裂中的作用及其作为治疗靶点的潜力。

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《Oncogene》 |2015年第14期|1758-1767|共10页
作者
Kreis N-N; Louwen F.; Yuan J.;
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Goethe Univ Frankfurt, Dept Gynecol & Obstet, D-60590 Frankfurt, Germany;

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正文语种英语
中图分类肿瘤学;
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1. p21 Waf1/Cip1 can protect human colon carcinoma cells against p53-dependent and p53-independent apoptosis induced by natural chemopreventive and therapeutic agents. [J] . Mahyar-Roemer M, Roemer K Oncogene . 2001,第26期

机译：p21 Waf1/Cip1 can protect human colon carcinoma cells against p53-dependent and p53-independent apoptosis induced by natural chemopreventive and therapeutic agents.
2. Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies [J] . Ilie M., Long-Mira E., Bence C.Butori C.Lassalle S.Bouhlel L.Fazzalari L.Zahaf K.Lalvee S.Washetine K.Mouroux J.Venissac N.Poudenx M.Otto J.Sabourin J. C.Marquette C. H.Hofman V.Hofman P. Annals of oncology: official journal of the European Society for Medical Oncology . 2016,第1期

机译：Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies
3. Discrepancies between FISH and immunohistochemistry for assessment of the ALK status are associated with ALK 'borderline'-positive rearrangements or a high copy number: a potential major issue for anti-ALK therapeutic strategies [J] . Ilie M. I., Bence C., Hofman V.Long-Mira E.Butori C.Bouhlel L.Lalvee S.Mouroux J.Poudenx M.Otto J.Marquette C. H.Hofman P. Annals of oncology: official journal of the European Society for Medical Oncology . 2015,第1期

机译：Discrepancies between FISH and immunohistochemistry for assessment of the ALK status are associated with ALK 'borderline'-positive rearrangements or a high copy number: a potential major issue for anti-ALK therapeutic strategies
4. Influence of Ras and Rho on p21~(Waf1/cip1) Protein Stability [C] . M. Coleman, C.J. Marshall and M.F. Olson NATO Advanced Study Institute on Molecular Mechanisms of Signal Transduction . 2000

机译：Ras和Rho对P21〜（WAF1 / CIP1）蛋白质稳定性的影响
5. The role of p21(Cip1) in n-butyrate-induced CD4+ T cell tolerance [D] . Dagtas, A. Selma 2006

机译：p21（Cip1）在正丁酸酯诱导的CD4 + T细胞耐受中的作用
6. Epidermal growth factor increases the level of the cyclin-dependent kinase (CDK) inhibitor p21/CIP1 (CDK-interacting protein 1) in A431 cells by increasing the half-lives of the p21/CIP1 transcript and the p21/CIP1 protein. [O] . L E Johannessen, S L Knardal, I H Madshus 1999

机译：表皮生长因子通过增加p21 / CIP1转录本和p21 / CIP1蛋白的半衰期来提高A431细胞中细胞周期蛋白依赖性激酶（CDK）抑制剂p21 / CIP1（CDK相互作用蛋白1）的水平。
7. Epidermal growth factor increases the level of the cyclin-dependent kinase (CDK) inhibitor p21/CIP1 (CDK-interacting protein 1) in A431 cells by increasing the half-lives of the p21/CIP1 transcript and the p21/CIP1 protein. [O] . Johannessen, L E, Knardal, S L, Madshus, I H 1999

机译：表皮生长因子通过增加p21 / CIP1转录本和p21 / CIP1蛋白的半衰期来提高A431细胞中细胞周期蛋白依赖性激酶（CDK）抑制剂p21 / CIP1（CDK相互作用蛋白1）的水平。

Less understood issues: p21(Cip1) in mitosis and its therapeutic potential

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