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https://www.readbyqxmd.com/read/28515316/dna-damage-induced-degradation-of-exo1-limits-dna-end-resection-to-ensure-accurate-dna-repair
#1
Nozomi Tomimatsu, Bipasha Mukherjee, Janelle Louise Harris, Francesca Ludovica Boffo, Molly Hardebeck, Patrick Ryan Potts, Kum Kum Khanna, Sandeep Burma
End resection of DNA double-strand breaks (DSBs) to generate 3'-single-stranded DNA facilitates DSB repair via error-free homologous recombination (HR) while stymieing repair by the error-prone non-homologous end joining (NHEJ) pathway. Activation of DNA end resection involves phosphorylation of the 5' to 3' exonuclease EXO1 by the phosphoinositide 3-kinase-like kinases ATM and ATR, and by the cyclin-dependent kinases 1 and 2. After activation, EXO1 must also be restrained in order to prevent over-resection which is known to hamper optimal HR and trigger global genomic instability...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28506875/deubiquitinase-usp33-is-negatively-regulated-by-%C3%AE-trcp-through-ubiquitin-dependent-proteolysis
#2
Qiao Cheng, Yukang Yuan, Lemin Li, Tingting Guo, Ying Miao, Ying Ren, Jin Liu, Qian Feng, Xiaofang Wang, Peng Zhao, Yibo Zuo, Liping Qian, Liting Zhang, Hui Zheng
Ubiquitin-mediated proteolysis regulates cellular levels of various proteins, and therefore plays important roles in controlling cell signaling and disease progression. The Skp1-Cul1-F-box ubiquitin ligase β-TrCP is recognized as an important negative regulator for numerous key signaling proteins. Recently, the deubiquitinases (DUBs) have turned out to be essential to regulate signaling pathways related to human diseases. However, whether β-TrCP is able to regulate the deubiquitinase family members remains largely unexplored...
May 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28494021/rice-black-streaked-dwarf-virus-p7-2-forms-a-scf-complex-through-binding-to-oryza-sativa-skp1-like-proteins-and-interacts-with-gid2-involved-in-the-gibberellin-pathway
#3
Tao Tao, Cui-Ji Zhou, Qian Wang, Xiang-Ru Chen, Qian Sun, Tian-Yu Zhao, Jian-Chun Ye, Ying Wang, Zong-Ying Zhang, Yong-Liang Zhang, Ze-Jian Guo, Xian-Bing Wang, Da-Wei Li, Jia-Lin Yu, Cheng-Gui Han
As a core subunit of the SCF complex that promotes protein degradation through the 26S proteasome, S-phase kinase-associated protein 1 (SKP1) plays important roles in multiple cellular processes in eukaryotes, including gibberellin (GA), jasmonate, ethylene, auxin and light responses. P7-2 encoded by Rice black streaked dwarf virus (RBSDV), a devastating viral pathogen that causes severe symptoms in infected plants, interacts with SKP1 from different plants. However, whether RBSDV P7-2 forms a SCF complex and targets host proteins is poorly understood...
2017: PloS One
https://www.readbyqxmd.com/read/28483055/the-improvement-of-salt-tolerance-in-transgenic-tobacco-by-overexpression-of-wheat-f-box-gene-tafba1
#4
Zhongxian Zhao, Guangqiang Zhang, Shumei Zhou, Yuanqing Ren, Wei Wang
F-box protein is a major subunit of the Skp1-Cullin-F-box (SCF) complex. We previously isolated an F-box gene from wheat, TaFBA1, and here we show that overexpression of TaFBA1 in transgenic plants under salt stress increases germination rate, root elongation, and biomass accumulation compared with WT plants. Improvements in the photosynthetic rate and its corresponding parameters were also found in the transgenic plants. These results suggest that overexpression of TaFBA1 improves salt stress tolerance in transgenic tobacco...
June 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28410577/a-candidate-rxlr-effector-from-plasmopara-viticola-can-elicit-immune-responses-in-nicotiana-benthamiana
#5
Jiang Xiang, Xinlong Li, Ling Yin, Yunxiao Liu, Yali Zhang, Junjie Qu, Jiang Lu
BACKGROUND: Diverse plant pathogens deliver effectors into plant cells to alter host processes. Oomycete pathogen encodes a large number of putative RxLR effectors which are likely to play a role in manipulating plant defense responses. The secretome of Plasmopara viticola (downy mildew of grapevine) contains at least 162 candidate RxLR effectors discovered in our recent studies, but their roles in infection and pathogenicity remain to be determined. Here, we characterize in depth one of the putative RxLR effectors, PvRxLR16, which has been reported to induce cell death in Nicotiana benthamiana in our previous study...
April 14, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28216227/nek7-protects-telomeres-from-oxidative-dna-damage-by-phosphorylation-and-stabilization-of-trf1
#6
Rong Tan, Satoshi Nakajima, Qun Wang, Hongxiang Sun, Jing Xue, Jian Wu, Sabine Hellwig, Xuemei Zeng, Nathan A Yates, Thomas E Smithgall, Ming Lei, Yu Jiang, Arthur S Levine, Bing Su, Li Lan
Telomeric repeat binding factor 1 (TRF1) is essential to the maintenance of telomere chromatin structure and integrity. However, how telomere integrity is maintained, especially in response to damage, remains poorly understood. Here, we identify Nek7, a member of the Never in Mitosis Gene A (NIMA) kinase family, as a regulator of telomere integrity. Nek7 is recruited to telomeres and stabilizes TRF1 at telomeres after damage in an ATM activation-dependent manner. Nek7 deficiency leads to telomere aberrations, long-lasting γH2AX and 53BP1 foci, and augmented cell death upon oxidative telomeric DNA damage...
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28197531/targeting-sox9-for-degradation-to-inhibit-chemoresistance-metastatic-spread-and-recurrence
#7
Aldwin Suryo Rahmanto, Fredrik J Swartling, Olle Sangfelt
Cancer cells with stem-like properties are believed to contribute to treatment resistance, dissemination, and recurrence. SOX9 controls stem cell plasticity and its deregulation may provide a basis for tumor progression. Here, we summarize our findings of targeted SOX9 destruction by SCF(FBW7) (Skp1/Cul1/F-box) in medulloblastoma and its potential for therapeutic intervention.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28196083/cacybp-sip-promotes-the-proliferation-of-colon-cancer-cells
#8
Huihong Zhai, Yongquan Shi, Xiong Chen, Jun Wang, Yuanyuan Lu, Faming Zhang, Zhengxiong Liu, Ting Lei, Daiming Fan
CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin. We found that CacyBP/SIP was expressed in a high percentage of colon cancer cells, but not in normal colonic surface epithelium...
2017: PloS One
https://www.readbyqxmd.com/read/28184929/e3-ubiquitin-ligase-fbw7%C3%AE-inhibits-cholangiocarcinoma-cell-proliferation-by-downregulating-c-myc-and-cyclin-e
#9
Ming Li, Ling Ouyang, Zhigang Zheng, Dan Xiang, Aijun Ti, Leihua Li, Yuzhen Dan, Chundong Yu, Wengang Li
FBW7 (F-box and WD repeat domain-containing 7), also known as CDC4, AGO and SEL10, is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase. It is a recognized tumor suppressor because it targets multiple oncoproteins for ubiquitination-mediated destruction and its mutations are frequently identified in a variety of human malignancies. However, the function of FBW7 in proliferation of cholangiocarcinoma (CCA) remains unknown...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28139700/the-crystal-structure-of-the-sgt1-skp1-complex-the-link-between-hsp90-and-both-scf-e3-ubiquitin-ligases-and-kinetochores
#10
Oliver Willhoft, Richard Kerr, Dipali Patel, Wenjuan Zhang, Caezar Al-Jassar, Tina Daviter, Stefan H Millson, Konstantinos Thalassinos, Cara K Vaughan
The essential cochaperone Sgt1 recruits Hsp90 chaperone activity to a range of cellular factors including SCF E3 ubiquitin ligases and the kinetochore in eukaryotes. In these pathways Sgt1 interacts with Skp1, a small protein that heterodimerizes with proteins containing the F-box motif. We have determined the crystal structure of the interacting domains of Saccharomyces cerevisiae Sgt1 and Skp1 at 2.8 Å resolution and validated the interface in the context of the full-length proteins in solution. The BTB/POZ domain of Skp1 associates with Sgt1 via the concave surface of its TPR domain using residues that are conserved in humans...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28115489/functional-validation-of-a-common-nonsynonymous-coding-variant-in-zc3hc1-associated-with-protection-from-coronary-artery-disease
#11
Tara Linseman, Sébastien Soubeyrand, Amy Martinuk, Majid Nikpay, Paulina Lau, Ruth McPherson
BACKGROUND: Although virtually all coronary artery disease associated single-nucleotide polymorphisms identified by genome-wide association studies (GWAS) are in noncoding regions of the genome, a common polymorphism in ZC3HC1 (rs11556924), resulting in an arginine (Arg) to histidine (His) substitution in its encoded protein, NIPA (Nuclear Interacting Partner of Anaplastic Lyphoma Kinase) is linked to a protection from coronary artery disease. NIPA plays a role in cell cycle progression, but the functional consequences of this polymorphism have not been established...
January 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28111017/structural-mimicry-by-a-bacterial-f-box-effector-hijacks-the-host-ubiquitin-proteasome-system
#12
Kathy Wong, John D Perpich, Guennadi Kozlov, Miroslaw Cygler, Yousef Abu Kwaik, Kalle Gehring
Ankyrin B (AnkB/LegAU13) is a translocated F box effector essential for the intracellular replication of the pathogen Legionella pneumophila. AnkB co-opts a host ubiquitin ligase to decorate the pathogen-containing vacuole with K(48)-linked polyubiquitinated proteins and degrade host proteins as a source of energy. Here, we report that AnkB commandeers the host ubiquitin-proteasome system through mimicry of two eukaryotic protein domains. Using X-ray crystallography, we determined the 3D structure of AnkB in complex with Skp1, a component of the human SCF ubiquitination ligase...
February 7, 2017: Structure
https://www.readbyqxmd.com/read/27956528/a-novel-function-of-f-box-protein-fbxo17-in-negative-regulation-of-type-i-ifn-signaling-by-recruiting-pp2a-for-ifn-regulatory-factor-3-deactivation
#13
Di Peng, Zining Wang, Anfei Huang, Yong Zhao, F Xiao-Feng Qin
The F-box proteins were originally identified as the key component of SKP1-Cullin1-F-box E3 ligase complexes that control the stability of their specific downstream substrates essential for cell growth and survival. However, the involvement of these proteins in type I IFN (IFN-I) signaling during innate immunity has not been investigated. In this study we report that the F-box protein FBXO17 negatively regulates IFN-I signaling triggered by double-strand DNA, RNA, or viral infection. We found that FBXO17 specifically interacts with IFN regulatory factor 3 (IRF3) and decreases its dimerization and nuclear translocation...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27932386/aberrant-expression-of-fbxo2-disrupts-glucose-homeostasis-through-ubiquitin-mediated-degradation-of-insulin-receptor-in-obese-mice
#14
Bin Liu, Han Lu, Duanzhuo Li, Xuelian Xiong, Lu Gao, Zhixiang Wu, Yan Lu
Insulin resistance is a critical factor in the development of metabolic disorders, including type 2 diabetes (T2DM). However, its molecular mechanisms remain incompletely understood. In the present study, we found that F-box only protein 2 (FBXO2), a substrate recognition component of SKP1-Cullin1-F-box protein (SCF) E3 ubiquitin ligase complex, were up-regulated in livers of obese mice. Furthermore, using a protein purification approach combined with high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS), we carried out a system-wide screening of FBXO2 substrates, in which insulin receptor (IR) was identified as a substrate for FBXO2...
December 8, 2016: Diabetes
https://www.readbyqxmd.com/read/27928637/molecular-functions-of-xanthomonas-type-iii-effector-avrbst-and-its-plant-interactors-in-cell-death-and-defense-signaling
#15
REVIEW
Sang Wook Han, Byung Kook Hwang
Xanthomonas effector AvrBsT interacts with plant defense proteins and triggers cell death and defense response. This review highlights our current understanding of the molecular functions of AvrBsT and its host interactor proteins. The AvrBsT protein is a member of a growing family of effector proteins in both plant and animal pathogens. Xanthomonas type III effector AvrBsT, a member of the YopJ/AvrRxv family, suppresses plant defense responses in susceptible hosts, but triggers cell death signaling leading to hypersensitive response (HR) and defense responses in resistant plants...
February 2017: Planta
https://www.readbyqxmd.com/read/27916606/fbx8-is-a-metastasis-suppressor-downstream-of-mir-223-and-targeting-mtor-for-degradation-in-colorectal-carcinoma
#16
F F Wang, X J Zhang, Y R Yan, X H Zhu, J Yu, Y Ding, J L Hu, W J Zhou, Z C Zeng, W T Liao, Y Q Ding, L Liang
F-box proteins are critical components of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases and involved in the ubiquitin-dependent proteolytic pathway. Dysregulation of F-box protein-mediated proteolysis often leads to human malignancies. F-box only protein 8 (FBX8), a novel component of F-box proteins, is down-regulated in several tumors and closely correlates with tumor progression. However, little is known about its function, regulatory mechanisms and substrates in the progression of colorectal carcinoma (CRC)...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27890708/fbxl18-targets-lrrk2-for-proteasomal-degradation-and-attenuates-cell-toxicity
#17
Xiaodong Ding, Sandeep K Barodia, Lisha Ma, Matthew S Goldberg
Dominantly inherited mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common causes of familial Parkinson's disease (PD) and LRRK2 polymorphisms are associated with increased risk for idiopathic PD. However, the molecular mechanisms by which these mutations cause PD remain uncertain. In vitro studies indicate that disease-linked mutations in LRRK2 increase LRRK2 kinase activity and LRRK2-mediated cell toxicity. Identifying LRRK2-interacting proteins and determining their effects on LRRK2 are important for understanding LRRK2 function and for delineating the pathophysiological mechanisms of LRRK2 mutations...
February 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27875300/the-fission-yeast-pre-mrna-processing-factor-18-prp18-has-intron-specific-splicing-functions-with-links-to-g1-s-cell-cycle-progression
#18
Nagampalli Vijaykrishna, Geetha Melangath, Rakesh Kumar, Piyush Khandelia, Pushpinder Bawa, Raghavan Varadarajan, Usha Vijayraghavan
The fission yeast genome, which contains numerous short introns, is an apt model for studies on fungal splicing mechanisms and splicing by intron definition. Here we perform a domain analysis of the evolutionarily conserved Schizosaccharomyces pombe pre-mRNA-processing factor, SpPrp18. Our mutational and biophysical analyses of the C-terminal α-helical bundle reveal critical roles for the conserved region as well as helix five. We generate a novel conditional missense mutant, spprp18-5 To assess the role of SpPrp18, we performed global splicing analyses on cells depleted of prp18(+) and the conditional spprp18-5 mutant, which show widespread but intron-specific defects...
December 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27855403/fbxo6-mediated-ubiquitination-and-degradation-of-ero1l-inhibits-endoplasmic-reticulum-stress-induced-apoptosis
#19
Xi Chen, Lang-Huan Duan, Peng-Cheng Luo, Gang Hu, Xin Yu, Jie Liu, Han Lu, Bin Liu
BACKGROUND/AIMS: FBXO6 is the substrate recognition component of a Skp1-Cullin1-F-box protein (SCF) ubiquitin E3 ligase complex, recognizing the chitobiose in unfolded N-glycoprotein to target glycoproteins for polyubiquitination and degradation. Although how FBXO6 recognizes glycoprotein has been fully investigated, the ubiquitination substrates of FBXO6 remain largely unknown. Previously, we have systematically identified the glycoproteins that interact with FBXO6 in an N-glycan dependent manner by LC/MS spectrum and confirmed the interaction between FBXO6 and glycosylated Ero1L, a protein disulfide oxidase in endoplasmic reticulum (ER)...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27835873/proteomic-identification-of-the-oncoprotein-stat3-as-a-target-of-a-novel-skp1-inhibitor
#20
Xin Cheng, Yong-Qiang Liu, Gui-Zhen Wang, Li-Na Yang, Yong-Zhi Lu, Xin-Chun Li, Bo Zhou, Li-Wei Qu, Xiao-Lu Wang, Yong-Xian Cheng, Jinsong Liu, Sheng-Ce Tao, Guang-Biao Zhou
The S phase kinase-associated protein 1 (Skp1), an adaptor protein of the Skp1-Cul1-F-box protein complex, binds the ubiquitin E3 ligase Skp2 and is critical to its biological functions. Targeting of Skp1 by a small compound 6-O-angeloylplenolin (6-OAP) results in dissociation and degradation of Skp2 and mitotic arrest of lung cancer cells. Here, by using a proteome microarray containing 16,368 proteins and a biotinylated 6-OAP, we identified 99 proteins that could bind 6-OAP, with Skp1 and STAT3 sitting at the central position of the 6-OAP interactome...
January 10, 2017: Oncotarget
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