• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

脯氨酰羟化酶结构域2在乳腺癌细胞生长和进展中的非经典功能：肽基脯氨酰顺反异构酶NIMA相互作用蛋白1的作用

Non-canonical Function of Prolyl Hydroxylase Domain 2 in Breast Cancer Cell Growth and Progression: Role of Peptidyl-prolyl Cis-trans Isomerase NIMA-interacting 1.

作者信息

Guillen-Quispe Yanymee N, Kim Su-Jung, Saeidi Soma, Choi Gyo-Jin, Chelakkot Chaithanya, Zhou Tianchi, Bang Sang-Beom, Kim Tae-Won, Shin Young Kee, Surh Young-Joon

机构信息

Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.

出版信息

J Cancer Prev. 2024 Dec 30;29(4):129-139. doi: 10.15430/JCP.24.031.

DOI:10.15430/JCP.24.031
PMID:39790223
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11706723/
Abstract

Prolyl hydroxylase domain 2 (PHD2) is the primary oxygen sensing enzyme involved in hydroxylation of hypoxia-inducible factor (HIF). Under normoxic conditions, PHD2 hydroxylates specific proline residues in HIF-1α and HIF-2α, promoting their ubiquitination and subsequent proteasomal degradation. Although PHD2 activity decreases in hypoxia, notable residual activity persists, but its function in these conditions remains unclear Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) targets proteins with phosphorylated serine/threonine-proline (pSer/Thr-Pro) motifs. As PHD2 contains several pSer/Thr-Pro motifs, it may be a potential substrate of Pin1. In the present study, we found Pin1 and PHD2 interactions in human breast cancer MDA-MB-231 cells. The breast cancer tissue array revealed higher levels of PHD2 and Pin1 in tumors compared to adjacent normal tissues. Through liquid chromatography-tandem mass spectrometry spectrometry, three phosphorylation sites (S125, T168, and S174) on PHD2 were identified, with serine 125 as the main site for Pin1 binding. As a new Pin1 binding partner, oncogenic PHD2 could be a potential therapeutic target for breast cancer treatment.

摘要

脯氨酰羟化酶结构域2（PHD2）是参与缺氧诱导因子（HIF）羟基化的主要氧传感酶。在常氧条件下，PHD2使HIF-1α和HIF-2α中的特定脯氨酸残基羟基化，促进其泛素化及随后的蛋白酶体降解。虽然在缺氧时PHD2活性降低，但仍存在显著的残余活性，但其在这些条件下的功能仍不清楚。肽基脯氨酰顺反异构酶NIMA相互作用蛋白1（Pin1）靶向具有磷酸化丝氨酸/苏氨酸-脯氨酸（pSer/Thr-Pro）基序的蛋白质。由于PHD2含有多个pSer/Thr-Pro基序，它可能是Pin1的潜在底物。在本研究中，我们在人乳腺癌MDA-MB-231细胞中发现了Pin1与PHD2的相互作用。乳腺癌组织芯片显示，与相邻正常组织相比，肿瘤中PHD2和Pin1的水平更高。通过液相色谱-串联质谱法，确定了PHD2上的三个磷酸化位点（S125、T168和S174），其中丝氨酸125是Pin1结合的主要位点。作为一种新的Pin1结合伴侣，致癌性PHD2可能是乳腺癌治疗的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/c5d12b8239b1/jcp-29-4-129-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/d7d1094c46e4/jcp-29-4-129-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/4b63fc5c5cba/jcp-29-4-129-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/98b430b4c2a1/jcp-29-4-129-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/b78ac1b00a49/jcp-29-4-129-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/53974ab07130/jcp-29-4-129-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/c5d12b8239b1/jcp-29-4-129-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/d7d1094c46e4/jcp-29-4-129-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/4b63fc5c5cba/jcp-29-4-129-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/98b430b4c2a1/jcp-29-4-129-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/b78ac1b00a49/jcp-29-4-129-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/53974ab07130/jcp-29-4-129-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751f/11706723/c5d12b8239b1/jcp-29-4-129-f6.jpg

相似文献

1
Non-canonical Function of Prolyl Hydroxylase Domain 2 in Breast Cancer Cell Growth and Progression: Role of Peptidyl-prolyl Cis-trans Isomerase NIMA-interacting 1.脯氨酰羟化酶结构域2在乳腺癌细胞生长和进展中的非经典功能：肽基脯氨酰顺反异构酶NIMA相互作用蛋白1的作用
J Cancer Prev. 2024 Dec 30;29(4):129-139. doi: 10.15430/JCP.24.031.
2
Oxygen-independent stabilization of HIF-2α in breast cancer through direct interaction with peptidyl-prolyl cis-trans isomerase NIMA-interacting 1.通过与肽基脯氨酰顺反异构酶 NIMA 相互作用蛋白 1 的直接相互作用，在乳腺癌中实现 HIF-2α 的氧独立性稳定。
Free Radic Biol Med. 2023 Oct;207:296-307. doi: 10.1016/j.freeradbiomed.2023.07.020. Epub 2023 Jul 19.
3
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 directly binds and stabilizes Nrf2 in breast cancer.肽基脯氨酰顺反异构酶 NIMA 相互作用蛋白 1 直接结合并稳定乳腺癌中的 Nrf2。
FASEB J. 2022 Jan;36(1):e22068. doi: 10.1096/fj.202100776RR.
4
The peptidyl prolyl cis/trans isomerase FKBP38 determines hypoxia-inducible transcription factor prolyl-4-hydroxylase PHD2 protein stability.肽基脯氨酰顺/反异构酶FKBP38决定缺氧诱导转录因子脯氨酰-4-羟化酶PHD2的蛋白质稳定性。
Mol Cell Biol. 2007 May;27(10):3758-68. doi: 10.1128/MCB.01324-06. Epub 2007 Mar 12.
5
The prolyl isomerase Pin1 regulates hypoxia-inducible transcription factor (HIF) activity.脯氨酰异构酶Pin1调节缺氧诱导转录因子（HIF）的活性。
Cell Signal. 2014 Aug;26(8):1649-56. doi: 10.1016/j.cellsig.2014.04.005. Epub 2014 Apr 12.
6
Role of phosphorylation in determining the backbone dynamics of the serine/threonine-proline motif and Pin1 substrate recognition.磷酸化在决定丝氨酸/苏氨酸-脯氨酸基序的主链动力学及Pin1底物识别中的作用。
Biochemistry. 1998 Apr 21;37(16):5566-75. doi: 10.1021/bi973060z.
7
Interaction between Peptidyl-prolyl - Isomerase NIMA-interacting 1 and GTP-H-Ras: Implications for Aggressiveness of Human Mammary Epithelial Cells and Drug Resistance.肽基脯氨酰异构酶NIMA相互作用蛋白1与GTP-H-Ras之间的相互作用：对人乳腺上皮细胞侵袭性和耐药性的影响
J Cancer Prev. 2020 Dec 30;25(4):234-243. doi: 10.15430/JCP.2020.25.4.234.
8
The Peptidyl-Prolyl isomerase, Pin1, associates with Protein Kinase C θ a critical Phospho-Thr-Pro motif in the V3 regulatory domain.肽基脯氨酰顺反异构酶 Pin1 与蛋白激酶 Cθ 结合，在 V3 调节域的关键磷酸化 Thr-Pro 基序中。
Front Immunol. 2023 Mar 8;14:1126464. doi: 10.3389/fimmu.2023.1126464. eCollection 2023.
9
Peptidyl Prolyl Isomerase PIN1 Directly Binds to and Stabilizes Hypoxia-Inducible Factor-1α.肽基脯氨酰异构酶PIN1直接结合并稳定缺氧诱导因子-1α。
PLoS One. 2016 Jan 19;11(1):e0147038. doi: 10.1371/journal.pone.0147038. eCollection 2016.
10
Prolyl Isomerase Pin1 in Human Cancer: Function, Mechanism, and Significance.人类癌症中的脯氨酰异构酶Pin1：功能、机制及意义
Front Cell Dev Biol. 2020 Mar 31;8:168. doi: 10.3389/fcell.2020.00168. eCollection 2020.

本文引用的文献

1
Oxygen-independent stabilization of HIF-2α in breast cancer through direct interaction with peptidyl-prolyl cis-trans isomerase NIMA-interacting 1.通过与肽基脯氨酰顺反异构酶 NIMA 相互作用蛋白 1 的直接相互作用，在乳腺癌中实现 HIF-2α 的氧独立性稳定。
Free Radic Biol Med. 2023 Oct;207:296-307. doi: 10.1016/j.freeradbiomed.2023.07.020. Epub 2023 Jul 19.
2
SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis.SIPA1通过HIF-2α途径增强有氧糖酵解以促进乳腺癌转移。
Front Cell Dev Biol. 2022 Jan 12;9:779169. doi: 10.3389/fcell.2021.779169. eCollection 2021.
3
The non-canonical functions of HIF prolyl hydroxylases and their dual roles in cancer.
HIF 脯氨酰羟化酶的非经典功能及其在癌症中的双重作用。
Int J Biochem Cell Biol. 2021 Jun;135:105982. doi: 10.1016/j.biocel.2021.105982. Epub 2021 Apr 21.
4
Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy.靶向Pin1调节细胞运动性及癌症治疗
Biomedicines. 2021 Mar 31;9(4):359. doi: 10.3390/biomedicines9040359.
5
Alternative regulation of HIF-1α stability through Phosphorylation on Ser451.通过丝氨酸 451 的磷酸化作用对 HIF-1α 稳定性进行的替代调节。
Biochem Biophys Res Commun. 2021 Mar 19;545:150-156. doi: 10.1016/j.bbrc.2021.01.047. Epub 2021 Feb 4.
6
Cysteine-113 covalency inspires the development of Pin1 inhibitor.半胱氨酸113的共价性推动了Pin1抑制剂的研发。
Signal Transduct Target Ther. 2020 Oct 6;5(1):225. doi: 10.1038/s41392-020-00339-9.
7
The peptidyl prolyl isomerase, PIN1 induces angiogenesis through direct interaction with HIF-2α.肽基脯氨酰顺反异构酶 PIN1 通过与 HIF-2α 的直接相互作用诱导血管生成。
Biochem Biophys Res Commun. 2020 Dec 17;533(4):995-1003. doi: 10.1016/j.bbrc.2020.08.015. Epub 2020 Oct 2.
8
Regulation of glycolysis by the hypoxia-inducible factor (HIF): implications for cellular physiology.缺氧诱导因子 (HIF) 对糖酵解的调节：对细胞生理学的影响。
J Physiol. 2021 Jan;599(1):23-37. doi: 10.1113/JP280572. Epub 2020 Oct 15.
9
Prolyl Isomerase Pin1 in Human Cancer: Function, Mechanism, and Significance.人类癌症中的脯氨酰异构酶Pin1：功能、机制及意义
Front Cell Dev Biol. 2020 Mar 31;8:168. doi: 10.3389/fcell.2020.00168. eCollection 2020.
10
Function of PIN1 in Cancer Development and Its Inhibitors as Cancer Therapeutics.PIN1在癌症发展中的作用及其抑制剂作为癌症治疗药物的研究
Front Cell Dev Biol. 2020 Mar 17;8:120. doi: 10.3389/fcell.2020.00120. eCollection 2020.