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Yikai Huang, Wukui Zhao, Congcong Wang, Yaru Zhu, Mengjie Liu, Huan Tong, Yin Xia, Qing Jiang, Jinzhong Qin
Though genetic data suggest that Polycomb group proteins (PcGs) are central chromatin modifiers and repressors that have been implicated in control of embryonic stem cell (ESC) pluripotency, the precise mechanism of PcG complex recruitment remains elusive, especially in mammals. We now report that the first and second MBT repeats of L3mbtl2 are important structural and functional features that are necessary and sufficient for L3mbtl2-mediated recruitment of PRC1.6 complex to target promoters. Interestingly, this region of L3mbtl2 harbors the evolutionarily conserved Pho-binding pocket also present in Drosophila Sfmbt, and mutation of the critical residues within this pocket completely abolishes its interaction with target promoters...
March 13, 2018: Cell Reports
Joseph E Gergely, Armond E Dorsey, Goberdhan P Dimri, Manjari Dimri
Polycomb group (PcG) protein BMI1 is an important regulator of oncogenic phenotype and is often overexpressed in several human malignancies including breast cancer. Aberrant expression of BMI1 is associated with metastasis and poor prognosis in cancer patients. At present, therapy reagents that can efficiently inhibit the expression of BMI1 are not very well known. Here, we report that Timosaponin A-III (TA-III), a steroidal saponin obtained from the rhizomes of an herb, Anemarrhena asphodeloides, strongly inhibits expression of BMI1 in breast cancer cells...
March 12, 2018: Molecular Carcinogenesis
(no author information available yet)
SS18-SSX usurps the PRC1.1 repressive complex to drive expression of a synovial sarcoma gene signature.
March 9, 2018: Cancer Discovery
Katherine R Parzych, Aileen Ariosa, Muriel Mari, Daniel J Klionsky
Macroautophagy (hereafter autophagy) is a cellular recycling pathway essential for cell survival during nutrient deprivation that culminates in the degradation of cargo within the vacuole in yeast and the lysosome in mammals, followed by efflux of the resultant macromolecules back into the cytosol. The yeast vacuole is home to many different hydrolytic proteins and while few have established roles in autophagy, the involvement of others remains unclear. The vacuolar serine carboxypeptidase Prc1 (carboxypeptidase Y) has not been previously shown to have a role in vacuolar zymogen activation and has not been directly implicated in the terminal degradation steps of autophagy...
March 7, 2018: Molecular Biology of the Cell
Huizhen Hu, Ran Zhang, Zhangsheng Tao, Xukai Li, Yuyang Li, Jiangfeng Huang, Xinxin Li, Xiao Han, Shengqiu Feng, Guimin Zhang, Liangcai Peng
Cellulose is the most characteristic component of plant cell walls and plays a central role in plant mechanical strength and morphogenesis. Despite cellulose synthase (CesA) mutants have exhibited a reduction of cellulose level, much remains unknown about their impacts on the cell growth (elongation and division) and cell wall integrity that fundamentally determine plant growth. Here, we examined three major types of AtCesAs mutants (rsw1, AtCesA1 mutant; prc1-1 and cesa6, AtCesA6-null mutants; IRX3, AtCesA7 mutant) and transgenic mutants that overexpressed AtCesAs genes in the background of AtCesA6-null mutants...
March 5, 2018: Plant & Cell Physiology
Peter W S Hill, Harry G Leitch, Cristina E Requena, Zhiyi Sun, Rachel Amouroux, Monica Roman-Trufero, Malgorzata Borkowska, Jolyon Terragni, Romualdas Vaisvila, Sarah Linnett, Hakan Bagci, Gopuraja Dharmalingham, Vanja Haberle, Boris Lenhard, Yu Zheng, Sriharsa Pradhan, Petra Hajkova
Gametes are highly specialized cells that can give rise to the next generation through their ability to generate a totipotent zygote. In mice, germ cells are first specified in the developing embryo around embryonic day (E) 6.25 as primordial germ cells (PGCs). Following subsequent migration into the developing gonad, PGCs undergo a wave of extensive epigenetic reprogramming around E10.5-E11.5, including genome-wide loss of 5-methylcytosine. The underlying molecular mechanisms of this process have remained unclear, leading to our inability to recapitulate this step of germline development in vitro...
March 7, 2018: Nature
Ana Banito, Xiang Li, Aimée N Laporte, Jae-Seok Roe, Francisco Sanchez-Vega, Chun-Hao Huang, Amanda R Dancsok, Katerina Hatzi, Chi-Chao Chen, Darjus F Tschaharganeh, Rohit Chandwani, Nilgun Tasdemir, Kevin B Jones, Mario R Capecchi, Christopher R Vakoc, Nikolaus Schultz, Marc Ladanyi, Torsten O Nielsen, Scott W Lowe
Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands...
February 22, 2018: Cancer Cell
Run-Shan Duan, Gang-Bin Tang, Hong-Zhen Du, Yi-Wen Hu, Pei-Pei Liu, Ya-Jie Xu, Yu-Qiang Zeng, Shuang-Feng Zhang, Rui-Ying Wang, Zhao-Qian Teng, Chang-Mei Liu
Neurons in the central nervous system (CNS) lose their intrinsic ability and fail to regenerate, but the underlying mechanisms are largely unknown. Polycomb group (PcG) proteins, which include PRC1 and PRC2 complexes function as gene repressors and are involved in many biological processes. Here we report that PRC1 components (polycomb chromobox (CBX) 2, 7, and 8) are novel regulators of axon growth and regeneration. Especially, knockdown of CBX7 in either embryonic cortical neurons or adult dorsal root ganglion (DRG) neurons enhances their axon growth ability...
February 19, 2018: Cell Death and Differentiation
Francoise S van Kampen, Marianne E Doornbos, Monique A van Rijn, Yolande den Bever
We report a patient with developmental delay due to germline AUTS2 mutation who developed a low-grade astrocytoma. While the contribution of this mutation to the pathogenesis of the tumor is not known at this time, a role of AUTS2 in deregulation of PRC1 can be a part in tumorigenesis of a brain tumor.
February 2018: Clinical Case Reports
Steffen Hanselmann, Patrick Wolter, Jonas Malkmus, Stefan Gaubatz
In this study, we investigated whether proteins that are involved in cytokinesis are potential targets for therapy of lung cancer. We find that the microtubule-associated protein PRC1 (protein required for cytokinesis 1), which plays a key role in organizing anti-parallel microtubule in the central spindle in cytokinesis, is overexpressed in lung cancer cell lines compared to normal cells. Increased expression of PRC1 is correlated with a poor prognosis of human lung adenocarcinoma patients. Lentiviral delivered, inducible RNAi of PRC1 demonstrated that proliferation of lung cancer cell lines strongly depends on PRC1...
January 12, 2018: Oncotarget
J Lesley Brown, Ming-An Sun, Judith A Kassis
Polycomb group (PcG) proteins maintain the silenced state of key developmental genes in animals, but how these proteins are recruited to specific regions of the genome is still poorly understood. In Drosophila , PcG proteins are recruited to Polycomb response elements (PREs) that include combinations of sites for sequence specific DNA binding "PcG recruiters," including Pho, Cg, and Spps. To understand their roles in PcG recruitment, we compared Pho-, Cg-, and Spps-binding sites against H3K27me3 and key PcG proteins by ChIP-seq in wild-type and mutant third instar larvae...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Su-Jie Ni, Li-Qin Zhao, Xiao-Feng Wang, Zhen-Hua Wu, Rui-Xi Hua, Chun-Hua Wan, Jie-Yun Zhang, Xiao-Wei Zhang, Ming-Zhu Huang, Lu Gan, Hua-Lin Sun, Goberdhan P Dimri, Wei-Jian Guo
BACKGROUND: Chromobox protein homolog 7 (CBX7), a member of the polycomb group (PcG) family of proteins, is involved in the regulation of cell proliferation and cancer progression. PcG family members, such as BMI, Mel-18, and EZH2, are integral constituents of the polycomb repressive complexes (PRCs) and have been known to regulate cancer stem cell (CSC) phenotype. However, the role of other PRCs' constituents such as CBX7 in the regulation of CSC phenotype remains largely elusive. This study was to investigate the role of CBX7 in regulating stem cell-like properties of gastric cancer and the underlying mechanisms...
February 8, 2018: Journal of Hematology & Oncology
Yong Jin Cho, Soo Hee Kim, Eun Kyung Kim, Jung Woo Han, Kyoo-Ho Shin, Hyuk Hu, Kyung Sik Kim, Young Deuk Choi, Sunghoon Kim, Young Han Lee, Jin-Suck Suh, Joong Bae Ahn, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha, Sung-Taek Jung, Hyo Song Kim
BACKGROUND: Polycomb repressive complex 2 (PRC2; formed by EZH2, SUZ12, and EED protein subunits) and PRC1 (BMI1 protein) induce gene silencing through histone modification by H3K27me3. In the present study, we characterized the PRC expression pattern and its clinical implication in sarcoma. METHODS: Using immunohistochemistry, we analyzed PRC expression in 105 sarcoma patients with 5 subtypes: synovial sarcoma (n = 18), rhabdomyosarcoma (n = 28), Ewing sarcoma (n = 15), osteosarcoma (n = 30), and others (n = 14)...
February 7, 2018: BMC Cancer
Jing Li, Marlene Dallmayer, Thomas Kirchner, Julian Musa, Thomas G P Grünewald
Cytokinesis is the final event of the cell cycle dividing one cell into two daughter cells. The protein regulator of cytokinesis (PRC)1 is essential for cytokinesis and normal cell cleavage. Deregulation of PRC1 causes cytokinesis defects that promote chromosomal instability (CIN) and thus tumor heterogeneity and cancer evolution. Consistently, abnormal PRC1 expression correlates with poor patient outcome in various malignancies, which may be caused by PRC1-mediated CIN and aneuploidy. Here, we review the physiological functions of PRC1 in cell cycle regulation and its contribution to tumorigenesis and intratumoral heterogeneity...
January 2018: Trends in Cancer
Sen Zhu, Dongyu Zhao, Lin Yan, Weihua Jiang, Jung-Sun Kim, Bingnan Gu, Qipeng Liu, Rui Wang, Bo Xia, Jonathan C Zhao, Gang Song, Wenyi Mi, Rong-Fu Wang, Xiaobing Shi, Hung-Ming Lam, Xuesen Dong, Jindan Yu, Kaifu Chen, Qi Cao
BMI1, a polycomb group (PcG) protein, plays a critical role in epigenetic regulation of cell differentiation and proliferation, and cancer stem cell self-renewal. BMI1 is upregulated in multiple types of cancer, including prostate cancer. As a key component of polycomb repressive complex 1 (PRC1), BMI1 exerts its oncogenic functions by enhancing the enzymatic activities of RING1B to ubiquitinate histone H2A at lysine 119 and repress gene transcription. Here, we report a PRC1-independent role of BMI1 that is critical for castration-resistant prostate cancer (CRPC) progression...
February 5, 2018: Nature Communications
Anna Palau, Anne-Kathrin Garz, Jeannine Diesch, Anabel Zwick, Roberto Malinverni, Vanesa Valero, Katrina Lappin, Raquel Casquero, Andreas Lennartsson, Johannes Zuber, Tomàs Navarro, Ken I Mills, Katharina S Götze, Marcus Buschbeck
Genetic lesions affecting epigenetic regulators are frequent in myelodysplastic syndromes (MDS). Polycomb proteins are key epigenetic regulators of differentiation and stemness that act as two multimeric complexes termed polycomb repressive complexes 1 and 2, PRC1 and PRC2, respectively. While components and regulators of PRC2 such as ASXL1 and EZH2 are frequently mutated in MDS and AML, little is known about the role of PRC1. To analyze the role of PRC1, we have taken a functional approach testing PRC1 components in loss- and gain-of-function experiments that we found overexpressed in advanced MDS patients or dynamically expressed during normal hematopoiesis...
December 29, 2017: Oncotarget
Bastian Stielow, Florian Finkernagel, Thorsten Stiewe, Andrea Nist, Guntram Suske
Diverse Polycomb repressive complexes 1 (PRC1) play essential roles in gene regulation, differentiation and development. Six major groups of PRC1 complexes that differ in their subunit composition have been identified in mammals. How the different PRC1 complexes are recruited to specific genomic sites is poorly understood. The Polycomb Ring finger protein PCGF6, the transcription factors MGA and E2F6, and the histone-binding protein L3MBTL2 are specific components of the non-canonical PRC1.6 complex. In this study, we have investigated their role in genomic targeting of PRC1...
January 30, 2018: PLoS Genetics
Hasan Rajabi, Masayuki Hiraki, Donald Kufe
The PRC2 and PRC1 complexes are aberrantly expressed in human cancers and have been linked to decreases in patient survival. MUC1-C is an oncoprotein that is also overexpressed in diverse human cancers and is associated with a poor prognosis. Recent studies have supported a previously unreported function for MUC1-C in activating PRC2 and PRC1 in cancer cells. In the regulation of PRC2, MUC1-C (i) drives transcription of the EZH2 gene, (ii) binds directly to EZH2, and (iii) enhances occupancy of EZH2 on target gene promoters with an increase in H3K27 trimethylation...
January 30, 2018: Oncogene
Shubhajit Mitra, Paige S Dunphy, Seema Das, Bing Zhu, Tian Luo, Jere W McBride
Ehrlichia chaffeensis has a group of well-characterized type I secreted tandem repeat protein (TRP) effectors that have moonlighting capabilities. TRPs modulate various cellular processes, reprogram host gene transcription as nucleomodulins, function as ubiquitin ligases, and directly activate conserved host cell signaling pathways to promote E. chaffeensis infection. One TRP interacting host target is polycomb group ring finger protein 5 (PCGF5), a member of the polycomb group (PcG) protein family, and a component of the polycomb repressive complex 1 (PRC1)...
January 22, 2018: Infection and Immunity
Baoyi Zhu, Mari Ekman, Daniel Svensson, Jessica Lindvall, Bengt-Olof Nilsson, Bengt Uvelius, Karl Swärd
Bladder denervation and bladder outlet obstruction are urological conditions that cause bladder growth. Transcriptomic surveys in outlet obstruction have identified differentially expressed genes, but similar studies following denervation have not been done. This was addressed using a rat model in which the pelvic ganglia were cryo-ablated followed by bladder microarray analyses. At 10 days following denervation, bladder weight had increased 5.6-fold and 2890 mRNAs and 135 miRNAs were differentially expressed...
January 10, 2018: American Journal of Physiology. Renal Physiology
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