Asp/ASPM在整个细胞周期中的磷酸化调控。

IF 2.3 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Genome Pub Date : 2024-10-29 DOI:10.1139/gen-2024-0111
Maria C Burns, Lori Borgal
{"title":"Asp/ASPM在整个细胞周期中的磷酸化调控。","authors":"Maria C Burns, Lori Borgal","doi":"10.1139/gen-2024-0111","DOIUrl":null,"url":null,"abstract":"<p><p>In mammals and <i>Drosophila melanogaster</i>, Asp/ASPM proteins contribute to cell proliferation and spindle formation. Recent evidence also suggests interphase roles for Asp/ASPM proteins, but little is known about the regulation allowing distinct roles in different cell cycle phases. In this review, we consider a cross-species comparison of Asp/ASPM protein sequences in light of cyclin-CDK literature, and suggest Asp/ASPM proteins to be prime candidates for cyclin-CDK regulation. Conserved regulatory features include an N-terminal proline directed serine/threonine (S/T-P) \"supershift\" phosphorylation domain common to proteins with bistable interphase and mitotic roles, as well as putative cyclin-binding sites positioned to allow multisite phosphorylation by cyclin-CDK complexes. Human, mouse, and <i>Drosophila</i> Asp/ASPM protein structural predictions show that multisite phosphorylation of the N-term supershift domain could alter the availability of CH-domains and HEAT-motifs, which can contribute to microtubule binding and protein aggregation likely required for spindle formation. Structural predictions of the smallest reported microcephaly patient truncation also emphasize the importance of the arrangement of these motifs. We position this <i>in silico</i> analysis within recent literature to build new hypotheses for Asp/ASPM regulation in interphase and mitosis, as well as de-regulation in microcephaly and cancer. We also highlight the utility of comparing structural/functional differences between human ASPM and <i>Drosophila</i> Asp to gain further insight.</p>","PeriodicalId":12809,"journal":{"name":"Genome","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Asp/ASPM phospho-regulation throughout the cell cycle.\",\"authors\":\"Maria C Burns, Lori Borgal\",\"doi\":\"10.1139/gen-2024-0111\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In mammals and <i>Drosophila melanogaster</i>, Asp/ASPM proteins contribute to cell proliferation and spindle formation. Recent evidence also suggests interphase roles for Asp/ASPM proteins, but little is known about the regulation allowing distinct roles in different cell cycle phases. In this review, we consider a cross-species comparison of Asp/ASPM protein sequences in light of cyclin-CDK literature, and suggest Asp/ASPM proteins to be prime candidates for cyclin-CDK regulation. Conserved regulatory features include an N-terminal proline directed serine/threonine (S/T-P) \\\"supershift\\\" phosphorylation domain common to proteins with bistable interphase and mitotic roles, as well as putative cyclin-binding sites positioned to allow multisite phosphorylation by cyclin-CDK complexes. Human, mouse, and <i>Drosophila</i> Asp/ASPM protein structural predictions show that multisite phosphorylation of the N-term supershift domain could alter the availability of CH-domains and HEAT-motifs, which can contribute to microtubule binding and protein aggregation likely required for spindle formation. Structural predictions of the smallest reported microcephaly patient truncation also emphasize the importance of the arrangement of these motifs. We position this <i>in silico</i> analysis within recent literature to build new hypotheses for Asp/ASPM regulation in interphase and mitosis, as well as de-regulation in microcephaly and cancer. We also highlight the utility of comparing structural/functional differences between human ASPM and <i>Drosophila</i> Asp to gain further insight.</p>\",\"PeriodicalId\":12809,\"journal\":{\"name\":\"Genome\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genome\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1139/gen-2024-0111\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genome","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1139/gen-2024-0111","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

在哺乳动物和黑腹果蝇中,Asp/ASPM 蛋白有助于细胞增殖和纺锤体的形成。最近的证据还表明,Asp/ASPM 蛋白在细胞间期发挥作用,但人们对其在不同细胞周期阶段发挥不同作用的调控机制知之甚少。在这篇综述中,我们根据细胞周期蛋白-CDK 文献对 Asp/ASPM 蛋白序列进行了跨物种比较,并认为 Asp/ASPM 蛋白是细胞周期蛋白-CDK 调控的主要候选蛋白。保守的调控特征包括具有双稳态间期和有丝分裂作用的蛋白质所共有的 N 端 S/T P "超移 "磷酸化结构域,以及假定的细胞周期蛋白结合位点,这些位点的定位允许细胞周期蛋白-CDK 复合物进行多位点磷酸化。人类、小鼠和果蝇的 Asp/ASPM 蛋白结构预测表明,N 端超移域的多位点磷酸化可能会改变 CH-位点和 HEAT-位点的可用性,而这些位点可能有助于微管结合和蛋白质聚集,这可能是纺锤体形成所必需的。对已报道的小头畸形患者最小截体的结构预测也强调了这些基序排列的重要性。我们将这一硅学分析与最近的文献结合起来,为Asp/ASPM在间期和有丝分裂中的调控以及在小头畸形和癌症中的去调控提出了新的假设。我们还强调了比较人类 ASPM 和果蝇 Asp 结构/功能差异的作用,以获得更深入的了解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Asp/ASPM phospho-regulation throughout the cell cycle.

In mammals and Drosophila melanogaster, Asp/ASPM proteins contribute to cell proliferation and spindle formation. Recent evidence also suggests interphase roles for Asp/ASPM proteins, but little is known about the regulation allowing distinct roles in different cell cycle phases. In this review, we consider a cross-species comparison of Asp/ASPM protein sequences in light of cyclin-CDK literature, and suggest Asp/ASPM proteins to be prime candidates for cyclin-CDK regulation. Conserved regulatory features include an N-terminal proline directed serine/threonine (S/T-P) "supershift" phosphorylation domain common to proteins with bistable interphase and mitotic roles, as well as putative cyclin-binding sites positioned to allow multisite phosphorylation by cyclin-CDK complexes. Human, mouse, and Drosophila Asp/ASPM protein structural predictions show that multisite phosphorylation of the N-term supershift domain could alter the availability of CH-domains and HEAT-motifs, which can contribute to microtubule binding and protein aggregation likely required for spindle formation. Structural predictions of the smallest reported microcephaly patient truncation also emphasize the importance of the arrangement of these motifs. We position this in silico analysis within recent literature to build new hypotheses for Asp/ASPM regulation in interphase and mitosis, as well as de-regulation in microcephaly and cancer. We also highlight the utility of comparing structural/functional differences between human ASPM and Drosophila Asp to gain further insight.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Genome
Genome 生物-生物工程与应用微生物
CiteScore
5.30
自引率
3.20%
发文量
42
审稿时长
6-12 weeks
期刊介绍: Genome is a monthly journal, established in 1959, that publishes original research articles, reviews, mini-reviews, current opinions, and commentaries. Areas of interest include general genetics and genomics, cytogenetics, molecular and evolutionary genetics, developmental genetics, population genetics, phylogenomics, molecular identification, as well as emerging areas such as ecological, comparative, and functional genomics.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信