Loss of tyrosine 211 phosphorylation of proliferating cell nuclear antigen (PCNA) enhances postnatal mammary gland development.

IF 2.1 Q2 MEDICINE, GENERAL & INTERNAL
BioMedicine-Taiwan Pub Date : 2024-09-01 eCollection Date: 2024-01-01 DOI:10.37796/2211-8039.1462
Yi-Chun Shen, You-Zhe Lin, Wan-Rong Wu, Pei-Le Lin, Chien-Ching Liao, Feng-Chi Chung, Chia-Yun Chen, Ching-Yu Weng, Shao-Chun Wang
{"title":"Loss of tyrosine 211 phosphorylation of proliferating cell nuclear antigen (PCNA) enhances postnatal mammary gland development.","authors":"Yi-Chun Shen, You-Zhe Lin, Wan-Rong Wu, Pei-Le Lin, Chien-Ching Liao, Feng-Chi Chung, Chia-Yun Chen, Ching-Yu Weng, Shao-Chun Wang","doi":"10.37796/2211-8039.1462","DOIUrl":null,"url":null,"abstract":"<p><p>The intricately orchestrated progression of mammary tissue development involves the precise coordination of gland differentiation and cellular proliferation. Nevertheless, the understanding of the role and regulatory mechanisms governing the DNA replication machinery in mammary gland development remains limited. Given the essential role of DNA replication in the viability of living cells, any genetic disturbance to its replicative function, in any form, will impede organ development. This circumstance poses a technical challenge in elucidating the potential function of cell proliferation in mammary morphogenesis. PCNA is crucial in DNA replication, playing a pivotal role in the development of complete eukaryotic organisms. The phosphorylation of PCNA at tyrosine 211 (Y211) has been demonstrated to play a significant role in supporting replication forks and, consequently, cell proliferation. Therefore, the utilization of a knock-in mouse model, wherein the Y211 residue of PCNA is replaced with phenylalanine (211F), presents an opportunity to evaluate the impact of reduced cell proliferation potential on mammary gland development. Interestingly, the lack of Y211 phosphorylation did not significantly impact the rates of proliferation or cell death in the mammary gland. In contrast, the absence of Y211PCNA led to an increased, rather than reduced, growth of the mammary gland. This was evident in assessments of gland length and the number of terminal end buds (TEBs) in both postnatal and virgin mammary glands. Notably, this observation correlated with an elevation in tissue stemness within the 211F glands compared to the WT glands. Additionally, it was consistent with the greater body weight gains observed in 211F pups compared to WT pups during the weaning period. Our findings unveil an unexpected aspect that may carry significance for mammary development. This newfound is associated with the regulation of a central component within the DNA replication machinery, providing insights into the intricate interplay governing mammary tissue expansion.</p>","PeriodicalId":51650,"journal":{"name":"BioMedicine-Taiwan","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460574/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BioMedicine-Taiwan","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.37796/2211-8039.1462","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0

Abstract

The intricately orchestrated progression of mammary tissue development involves the precise coordination of gland differentiation and cellular proliferation. Nevertheless, the understanding of the role and regulatory mechanisms governing the DNA replication machinery in mammary gland development remains limited. Given the essential role of DNA replication in the viability of living cells, any genetic disturbance to its replicative function, in any form, will impede organ development. This circumstance poses a technical challenge in elucidating the potential function of cell proliferation in mammary morphogenesis. PCNA is crucial in DNA replication, playing a pivotal role in the development of complete eukaryotic organisms. The phosphorylation of PCNA at tyrosine 211 (Y211) has been demonstrated to play a significant role in supporting replication forks and, consequently, cell proliferation. Therefore, the utilization of a knock-in mouse model, wherein the Y211 residue of PCNA is replaced with phenylalanine (211F), presents an opportunity to evaluate the impact of reduced cell proliferation potential on mammary gland development. Interestingly, the lack of Y211 phosphorylation did not significantly impact the rates of proliferation or cell death in the mammary gland. In contrast, the absence of Y211PCNA led to an increased, rather than reduced, growth of the mammary gland. This was evident in assessments of gland length and the number of terminal end buds (TEBs) in both postnatal and virgin mammary glands. Notably, this observation correlated with an elevation in tissue stemness within the 211F glands compared to the WT glands. Additionally, it was consistent with the greater body weight gains observed in 211F pups compared to WT pups during the weaning period. Our findings unveil an unexpected aspect that may carry significance for mammary development. This newfound is associated with the regulation of a central component within the DNA replication machinery, providing insights into the intricate interplay governing mammary tissue expansion.

增殖细胞核抗原(PCNA)的酪氨酸 211 磷酸化缺失会促进出生后乳腺的发育。
乳腺组织的发育过程错综复杂,涉及腺体分化和细胞增殖的精确协调。然而,人们对 DNA 复制机制在乳腺发育中的作用和调控机制的了解仍然有限。鉴于 DNA 复制对活细胞的存活起着至关重要的作用,对其复制功能的任何形式的遗传干扰都会阻碍器官的发育。这种情况对阐明细胞增殖在乳腺形态发生中的潜在功能提出了技术挑战。PCNA 在 DNA 复制中至关重要,在完整真核生物的发育过程中发挥着关键作用。PCNA 在酪氨酸 211 (Y211) 处的磷酸化已被证实在支持复制叉以及细胞增殖方面发挥着重要作用。因此,利用PCNA的Y211残基被苯丙氨酸(211F)取代的基因敲入小鼠模型,为评估细胞增殖潜力下降对乳腺发育的影响提供了机会。有趣的是,缺乏 Y211 磷酸化对乳腺的增殖率或细胞死亡率没有显著影响。相反,Y211PCNA 的缺失导致乳腺的生长增加而不是减少。这在产后乳腺和原始乳腺的腺体长度和末端芽(TEB)数量评估中都很明显。值得注意的是,与 WT 乳腺相比,这一观察结果与 211F 乳腺中组织干的增加有关。此外,与WT幼崽相比,211F幼崽在断奶期间的体重增加也更大。我们的发现揭示了一个意想不到的方面,它可能对乳腺发育具有重要意义。这一新发现与 DNA 复制机制中一个核心部件的调控有关,为乳腺组织扩张的复杂相互作用提供了启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
BioMedicine-Taiwan
BioMedicine-Taiwan MEDICINE, GENERAL & INTERNAL-
CiteScore
2.80
自引率
5.90%
发文量
21
审稿时长
24 weeks
×
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