MCRS1

更新于：2025-05-07

基本信息

别名

58 kDa microspherule protein、Cell cycle-regulated factor p78、ICP22BP

+ [7]

简介

Modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus (PubMed:11948183). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. May also be an inhibitor of TERT telomerase activity (PubMed:15044100). Binds to G-quadruplex structures in mRNA (PubMed:16571602). Binds to RNA homomer poly(G) and poly(U) (PubMed:16571602).

关联

100 项与 MCRS1 相关的临床结果

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100 项与 MCRS1 相关的转化医学

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0 项与 MCRS1 相关的专利（医药）

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项与 MCRS1 相关的文献（医药）

2024-12-02·Journal of Experimental Medicine

MCRS1 sensitizes T cell–dependent immunotherapy by augmenting MHC-I expression in solid tumors

Article

作者: Yi, Han ; Zhou, Zichu ; Wang, Jin ; Zhu, Sijing ; Zhong, Jiang ; Yang, Yulong ; Yan, Runhe ; Jiang, Ning ; Jin, Zheyu ; Jiang, Kaitao ; Liu, Yanfang ; Xiang, Qian ; Xue, Kangkang ; Dong, Yuchao ; Lin, Xinhua ; Ding, Chen ; Qian, Yuping ; Li, Xue ; Yu, Wei ; Sun, Shenfei ; Yu, Xiaofei ; Li, Kai

Dampened antigen presentation underscores the resistance of pancreatic cancer to T cell–mediated anti-tumor immunity, rendering immunotherapy largely ineffective. By high-throughput CRISPR activation perturbation, we discovered that the transcriptional regulator MCRS1 significantly augmented the sensitivity of mouse pancreatic cancer cells to T cell immunity in vitro and in vivo. Mechanistically, MCRS1 interacted with the transcription factor and genome organizer YY1 to coordinately increase the chromatin accessibility and expression of MHC-I genes. Elevated MCRS1 subverted MHC-I suppression and activated anti-tumor T cells, which sensitized mouse pancreatic cancer to α-PD-1 therapy. Remarkably, high MCRS1 expression was associated with increased T cell infiltration and extended survival of patients with pancreatic cancer and was predictive of favorable responses to α-PD-1 therapy in patients with lung cancer. Together, our study uncovers that MCRS1 sensitizes cancer cells to T cell immunity by transcriptionally subverting MHC-I suppression, which enhances the effectiveness of α-PD-1 therapy in mice and humans, paving the way to further improve immunotherapy against solid tumors.

2024-01-01·Advances in Biological Regulation

Proteomic and yeast 2-hybrid screens to identify PTEN binding partners

Article

作者: Spinelli, Laura ; Maccario, Helene ; Tibarewal, Priyanka ; Leslie, Nick R

PTEN is a phosphoinositide lipid phosphatase and an important tumour suppressor protein. PTEN function is reduced or lost in around a third of all human cancers through diverse mechanisms, from gene deletion to changes in the function of proteins which regulate PTEN through direct protein binding. Here we present data from SILAC (Stable Isotope Labelling by Amino acids in Cell culture) proteomic screens to identify proteins which bind to PTEN. These experiments using untransformed epithelial cells and glioma cells identified several novel candidate proteins in addition to many previously identified PTEN binding partners and many proteins which are recognised as common false positives using these methods. From subsequent co-expression pull-down experiments we provide further evidence supporting the physical interaction of PTEN with MMP1, Myosin 18A and SHROOM3. We also performed yeast two-hybrid screens which identify the previously recognised PTEN binding partner MSP58 in addition to the nuclear import export receptor TNPO3. These experiments identify several novel candidate binding partners of PTEN and provide further data addressing the set of proteins that interact with this important tumour suppressor.

2023-05-04·EMBO reports

Mcrs1 regulates G2/M transition and spindle assembly during mouse oocyte meiosis

Article

作者: Ji, Yi-Ming ; Zhang, Kun-Huan ; Pan, Zhen-Nan ; Sun, Shao-Chen ; Ju, Jia-Qian ; Liu, Jing-Cai

AbstractMicrospherule protein 1 (Mcrs1) is a component of the nonspecific lethal (NSL) complex and the chromatin remodeling INO80 complex, which participates in transcriptional regulation during mitosis. Here, we investigate the roles of Mcrs1 during female meiosis in mice. We demonstrate that Mcrs1 is a novel regulator of the meiotic G2/M transition and spindle assembly in mouse oocytes. Mcrs1 is present in the nucleus and associates with spindle poles and chromosomes of oocytes during meiosis I. Depletion of Mcrs1 alters HDAC2‐mediated H4K16ac, H3K4me2, and H3K9me2 levels in nonsurrounded nucleolus (NSN)‐type oocytes, and reduces CDK1 activity and cyclin B1 accumulation, leading to G2/M transition delay. Furthermore, Mcrs1 depletion results in abnormal spindle assembly due to reduced Aurora kinase (Aurka and Aurkc) and Kif2A activities, suggesting that Mcrs1 also plays a transcription‐independent role in regulation of metaphase I oocytes. Taken together, our results demonstrate that the transcription factor Mcrs1 has important roles in cell cycle regulation and spindle assembly in mouse oocyte meiosis.

项与 MCRS1 相关的新闻（医药）

2024-11-25

·生物谷

Journal of Experimental Medicine | 复旦大学于肖飞团队揭示增强实体瘤免疫敏感性的全新靶基因

T细胞免疫反应是人体清除肿瘤细胞的关键机制，它通过识别肿瘤细胞表面的MHC分子进而杀伤肿瘤细胞[1]。但肿瘤细胞具有多种机制逃逸免疫监视，限制T细胞的杀伤功能，其中包括降低抗原呈递、形成抑制性免疫微环境等[2]，这些机制同时也是影响免疫检查点抑制剂（ICB）疗法的关键因素。胰腺癌作为代表性的“冷肿瘤”，由于肿瘤细胞的低突变负荷、低抗原递呈的特点，阻碍了T细胞浸润与激活，导致其对免疫疗法响应较差[3-5]。因此，寻找新的靶点进而增强免疫治疗效果，延长患者生存期，具有极其重要的意义。 2024年11月15日，复旦大学生命科学学院于肖飞团队在免疫学权威期刊Journal of Experimental Medicine发表了题为MCRS1 sensitizes T cell-dependent immunotherapy by augmenting MHC-I expression in solid tumors的研究论文。该研究从胰腺癌出发，揭示了MCRS1在实体瘤中能够通过上调MHC-I分子表达，增强肿瘤细胞对T细胞杀伤的敏感性，同时改善PD-1阻断疗法的治疗效果。研究团队利用CRISPR激活（CRISPRa）筛选技术，在小鼠胰腺癌细胞（HT）中进行单基因扰动和体外杀伤筛选，并结合TCGA数据库及胰腺癌临床病理样本分析，鉴定出Mcrs1这一能够增强HT细胞对杀伤敏感性的候选基因。通过体内外实验发现，Mcrs1高表达可提高肿瘤细胞中MHC-I分子的表达水平和肿瘤浸润性T淋巴细胞的激活。通过ChIP-Seq、IP-MS及ATAC-Seq分析，发现MCRS1结合于MHC-I基因座，并与另一转录因子YY1相互作用进而协同调控染色质可及性和MHC-I的表达（图1）。同时，Mcrs1高表达也可以增强PD-1阻断对小鼠胰腺癌的治疗效果。临床数据分析表明，MCRS1高表达与胰腺癌患者总生存时间呈正相关。在非小细胞肺癌患者中， MCRS1高表达的患者同样也展现出了更好的PD-1阻断的治疗效果，这表明MCRS1可能在多种实体瘤中都具有相似的免疫增敏效果，具有作为临床中预测PD-1阻断治疗疗效的新指标的潜力。图1. MCRS1与YY1协同调控肿瘤抗原递呈和抗肿瘤免疫综上所述，该研究阐明了MCRS1调控肿瘤MHC-I表达的全新机制，MCRS1高表达的免疫增敏效应可以提高ICB的治疗效果，实现了肿瘤的由“冷”转“热”，为增强肿瘤免疫治疗效果提供了新靶点与新思路。复旦大学生命科学学院、遗传工程国家重点实验室、复旦大学张江研究院于肖飞研究员为最后通讯作者，海军军医大学第一附属医院刘艳芳副教授为共同通讯作者，并得到呼吸与危重症医学科董宇超主任的大力支持。复旦大学生命科学学院博士后李雪、博士生依含、金哲宇，硕士生蒋凯韬同学为该论文的共同第一作者。本研究受到国家基金委面上项目、上海市科委“原创探索”项目以及免疫与炎症全国重点实验室开放课题的资助。文章链接： https://doi.org/10.1084/jem.20240959 原文链接： https://life.fudan.edu.cn/b1/a1/c28140a700833/page.htm 参考文献： 1. Mellman, I., et al., The cancer-immunity cycle: Indication, genotype, and immunotype. Immunity, 2023. 56(10): p. 2188-2205. 2. Fenis, A., et al., New immune cell engagers for cancer immunotherapy. Nat Rev Immunol, 2024. 24(7): p. 471-486. 3. Yamamoto, K., et al., Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature, 2020. 581(7806): p. 100-105. 4. Zhong, W., et al., Comparison of the molecular and cellular phenotypes of common mouse syngeneic models with human tumors. BMC Genomics, 2020. 21(1): p. 2. 5. Maleki Vareki, S., High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors. J Immunother Cancer, 2018. 6(1): p. 157. 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

免疫疗法细胞疗法