4.7 Article

Cytosolic carboxypeptidase CCP6 is required for megakaryopoiesis by modulating Mad2 polyglutamylation

期刊

JOURNAL OF EXPERIMENTAL MEDICINE
卷 211, 期 12, 页码 2439-2454

出版社

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20141123

关键词

-

资金

  1. Chinese Academy of Sciences [XDA01010407, XDA01020203]
  2. National Natural Science Foundation of China [81330047, 30830030, 31372404]
  3. National Key Basic Research Program of China [2010CB911902, 2014CB964601]
  4. Chinese Academy of Sciences
  5. China Postdoctoral Science Foundation [20110490617, 2012T50145]

向作者/读者索取更多资源

Bone marrow progenitor cells develop into mature megakaryocytes (MKs) to produce platelets for hemostasis and other physiological functions. However, the molecular mechanisms underlying megakaryopoiesis are not completely defined. We show that cytosolic carboxy-peptidase (CCP) 6 deficiency in mice causes enlarged spleens and increased platelet counts with underdeveloped MKs and dysfunctional platelets. The prominent phenotypes of CCP6 deficiency are different from those of CCP1-deficient mice. We found that CCP6 and tubulin tyrosine ligase-like family (TTLL) members TTLL4 and TTLL6 are highly expressed in MKs. We identify Mad2 (mitotic arrest deficient 2) as a novel substrate for CCP6 and not CCP1. Mad2 can be polyglutamylated by TTLL4 and TTLL6 to modulate the maturation of MKs. CCP6 deficiency causes hyperglutamylation of Mad2 to promote activation of Aurora B, leading to suppression of MK maturation. We reveal that Mad2 polyglutamylation plays a critical role in the regulation of megakaryopoiesis.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Critical Care Medicine

Senescence of Alveolar Type 2 Cells Drives Progressive Pulmonary Fibrosis

Changfu Yao, Xiangrong Guan, Gianni Carraro, Tanyalak Parimon, Xue Liu, Guanling Huang, Apoorva Mulay, Harmik J. Soukiasian, Gregory David, Stephen S. Weigt, John A. Belperio, Peter Chen, Dianhua Jiang, Paul W. Noble, Barry R. Stripp

Summary: The study demonstrates that senescence of AT2 cells is sufficient to drive progressive pulmonary fibrosis, and interventions targeting p53 activation or senescence can block fibrogenesis. Early attenuation of senescence-related pathways and elimination of senescent cells are promising therapeutic approaches to prevent pulmonary fibrosis.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2021)

Article Immunology

Circular RNA circZbtb20 maintains ILC3 homeostasis and function via Alkbh5-dependent m6A demethylation of Nr4a1 mRNA

Benyu Liu, Nian Liu, Xiaoxiao Zhu, Liuliu Yang, Buqing Ye, Huimu Li, Pingping Zhu, Tiankun Lu, Yong Tian, Zusen Fan

Summary: The newly identified circular RNA circZbtb20 is crucial for the maintenance and function of group 3 innate lymphoid cells (ILC3), with its deletion causing reduced ILC3 numbers and increased susceptibility to bacterial infections. The circZbtb20 enhances the stability of specific mRNA and initiates a signaling pathway to maintain the homeostasis of ILC3.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

Article Medicine, Research & Experimental

Antibody-mediated depletion of CCR10+EphA3+ cells ameliorates fibrosis in IPF

Miriam S. Hohmann, David M. Habiel, Milena S. Espindola, Guanling Huang, Isabelle Jones, Rohan Narayanan, Ana Lucia Coelho, Justin M. Oldham, Imre Noth, Shwu-Fan Ma, Adrianne Kurkciyan, Jonathan L. McQualter, Gianni Carraro, Barry Stripp, Peter Chen, Dianhua Jiang, Paul W. Noble, William Parks, John Woronicz, Geoffrey Yarranton, Lynne A. Murray, Cory M. Hogaboam

Summary: IPF is characterized by elevated levels of CCR10 and CCL28 in lung tissue, with CCR10(+) cells promoting pulmonary fibrosis and EphA3 mAb targeting these cells reducing fibrosis.

JCI INSIGHT (2021)

Article Multidisciplinary Sciences

Categorization of lung mesenchymal cells in development and fibrosis

Xue Liu, Simon C. Rowan, Jiurong Liang, Changfu Yao, Guanling Huang, Nan Deng, Ting Xie, Di Wu, Yizhou Wang, Ankita Burman, Tanyalak Parimon, Zea Borok, Peter Chen, William C. Parks, Cory M. Hogaboam, S. Samuel Weigt, John Belperio, Barry R. Stripp, Paul W. Noble, Dianhua Jiang

Summary: Pulmonary mesenchymal cells play critical roles in lung development and disease states in both mice and humans, showing high heterogeneity and subtype-specific transcriptomic differences which contribute to matrix gene expression in fibrosis. Comparative analysis reveals conserved transcriptomic signatures in orthologous subpopulations of murine and human lung mesenchymal cells, enhancing our understanding of mesenchymal cell diversity in lung development and disease conditions.

ISCIENCE (2021)

Article Cell Biology

Global profiling of RNA-binding protein target sites by LACE-seq

Ruibao Su, Li-Hua Fan, Changchang Cao, Lei Wang, Zongchang Du, Zhaokui Cai, Ying-Chun Ouyang, Yue Wang, Qian Zhou, Ligang Wu, Nan Zhang, Xiaoxiao Zhu, Wen-Long Lei, Hailian Zhao, Yong Tian, Shunmin He, Catherine C. L. Wong, Qing-Yuan Sun, Yuanchao Xue

Summary: The LACE-seq method developed by Xue and colleagues allows for comprehensive profiling of RNA-binding protein targets at single-nucleotide resolution in low-input cells, shedding light on the essential functions of RBPs in germline and early embryo development. The precise mapping of RBP-binding sites in low-input cells opens up new avenues for studying the roles of RBPs in embryonic development and reproductive diseases.

NATURE CELL BIOLOGY (2021)

Article Multidisciplinary Sciences

Mesenchymal growth hormone receptor deficiency leads to failure of alveolar progenitor cell function and severe pulmonary fibrosis

Ting Xie, Vrishika Kulur, Ningshan Liu, Nan Deng, Yizhou Wang, Simon Coyle Rowan, Changfu Yao, Guanling Huang, Xue Liu, Forough Taghavifar, Jiurong Liang, Cory Hogaboam, Barry Stripp, Peter Chen, Dianhua Jiang, Paul W. Noble

Summary: Recent studies have shown that impaired renewal of type 2 alveolar epithelial cells (ATII) in IPF patients and mice with defective ATII can lead to severe pulmonary fibrosis. Growth hormone receptor (GHR) expression, mainly found in mesenchymal cells, is significantly decreased in IPF lungs, but higher levels of GHR expression are associated with better lung function in IPF patients. The findings suggest that a previously unidentified mesenchymal paracrine signaling via GHR can support ATII progenitor cell renewal and limit the severity of lung fibrosis.

SCIENCE ADVANCES (2021)

Article Biochemistry & Molecular Biology

An overview in the development of cathode materials for the improvement in power generation of microbial fuel cells

Song Qiu, Zhenyu Guo, Faiza Naz, Zhao Yang, Changyuan Yu

Summary: This review discusses the utilization, development, and cost of cathode materials in MFCs, highlighting effective modification methods that have led to improved power generation in recent years.

BIOELECTROCHEMISTRY (2021)

Article Biochemistry & Molecular Biology

Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via Hedgehog signaling

Yang Gu, Yanying Wang, Luyun He, Jiahang Zhang, Xiaoxiao Zhu, Nian Liu, Jianyi Wang, Tiankun Lu, Lei He, Yong Tian, Zusen Fan

Summary: This study identified circIPO11 as highly expressed in HCC tumor tissues and liver CSCs, playing a critical role in self-renewal maintenance of liver CSCs and HCC development. Mechanistically, circIPO11 activates the Hedgehog signaling pathway, promoting tumor cell propagation. Targeting circIPO11 and the Hedgehog pathway may provide new potential for HCC treatment.

MOLECULAR CANCER (2021)

Article Biochemistry & Molecular Biology

Discovery of potent and versatile CRISPR-Cas9 inhibitors engineered for chemically controllable genome editing

Guoxu Song, Fei Zhang, Chunhong Tian, Xing Gao, Xiaoxiao Zhu, Dongdong Fan, Yong Tian

Summary: This study identified novel anti-CRISPR families that have the ability to inhibit Cas9 activity and even control genome editing post-translationally. By studying different Acr variants and developing chemically inducible control, new avenues for CRISPR-Cas9 applications have been established.

NUCLEIC ACIDS RESEARCH (2022)

Article Multidisciplinary Sciences

N-1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism

Yanying Wang, Jing Wang, Xiaoyu Li, Xushen Xiong, Jianyi Wang, Ziheng Zhou, Xiaoxiao Zhu, Yang Gu, Dan Dominissini, Lei He, Yong Tian, Chengqi Yi, Zusen Fan

Summary: The study reveals elevated m(1)A methylation levels in hepatocellular carcinoma (HCC) patient tumour tissues and liver cancer stem cells, mediated by the TRMT6/TRMT61A complex. The inhibition of m(1)A methylation can decrease tumourigenesis.

NATURE COMMUNICATIONS (2021)

Article Immunology

Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine

Zhen Xiong, Xiaoxiao Zhu, Jingjing Geng, Yuwei Xu, Runyuan Wu, Cunzhen Li, Dongdong Fan, Xiwen Qin, Ying Du, Yong Tian, Zusen Fan

Summary: This study surveyed the acceptance and concerns regarding mRNA vaccines among participants from the United States and China, revealing differences in attitudes between the two countries. The study suggests strengthening public awareness and education to enhance people's knowledge and acceptance of mRNA vaccines.

IMMUNITY (2022)

Article Medicine, Research & Experimental

The ZIP8/SIRT1 axis regulates alveolar progenitor cell renewal in aging and idiopathic pulmonary fibrosis

Jiurong Liang, Guanling Huang, Xue Liu, Forough Taghavifar, Ningshan Liu, Yizhou Wang, Nan Deng, Changfu Yao, Ting Xie, Vrishika Kulur, Kristy Dai, Ankita Burman, Simon C. Rowan, S. Samuel Weigt, John Belperio, Barry Stripp, William C. Parks, Dianhua Jiang, Paul W. Noble

Summary: This study identified a deficiency of the zinc transporter SLC39A8 (ZIP8) in Type 2 alveolar epithelial cells (AEC2s) from both idiopathic pulmonary fibrosis (IPF) lungs and lungs of old mice, which is associated with impaired AEC2 renewal capacity and enhanced lung fibrosis. The regulation of AEC2 progenitor function by ZIP8 is dependent on SIRT1. Replenishment with exogenous zinc and activation of SIRT1 promote self-renewal and differentiation of AEC2s, and therapeutic strategies targeting zinc metabolism and SIRT1 signaling could potentially improve AEC2 progenitor function and mitigate fibrogenesis.

JOURNAL OF CLINICAL INVESTIGATION (2022)

Article Cell Biology

Gut microbiota drives macrophage-dependent self-renewal of intestinal stem cells via niche enteric serotonergic neurons

Pingping Zhu, Tiankun Lu, Jiayi Wu, Dongdong Fan, Benyu Liu, Xiaoxiao Zhu, Hui Guo, Ying Du, Feng Liu, Yong Tian, Zusen Fan

Summary: This study reveals how microbiota and the intestinal environment coordinately regulate intestinal stem cells through the activation of enteric serotonergic neurons and the promotion of specific signaling pathways between cells. These findings provide a new perspective for understanding the regulation mechanism of intestinal stem cells.

CELL RESEARCH (2022)

Article Immunology

Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity

Buqing Ye, Liuliu Yang, Benyu Liu, Nian Liu, Dongdong Fan, Huimu Li, Lei Sun, Ying Du, Shuo Wang, Yong Tian, Zusen Fan

Summary: This study demonstrates that thymidine can induce transdifferentiation of mouse fibroblasts into neutrophils, which exhibit antibacterial effects and can cure neutropenia in mice.

CELLULAR & MOLECULAR IMMUNOLOGY (2022)

Review Oncology

Cancer stem cells: a major culprit of intra-tumor heterogeneity

Faiza Naz, Mengran Shi, Salvia Sajid, Zhao Yang, Changyuan Yu

Summary: Cancer is characterized by heterogeneity, primarily caused by cancer stem cells that can be transformed by both intrinsic and extrinsic factors to intensify the aggressiveness of cancer cells. Understanding the intrinsic and extrinsic factors that influence cancer stem cell heterogeneity is crucial for intervening in these processes to ultimately improve cancer research and management.

AMERICAN JOURNAL OF CANCER RESEARCH (2021)

暂无数据