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https://www.readbyqxmd.com/read/28797197/dysregulated-expression-of-skp2-and-its-role-in-hematological-malignancies
#1
Michal Kulinski, Iman W Achkar, Mohammad Haris, Said Dermime, Ramzi R Mohammad, Shahab Uddin
S-phase kinase-associated protein 2 (SKP2) is a well-studied F-box protein and a critical part of the Skp1-Cul1-Fbox (SCF) E3 ligase complex. It controls cell cycle by regulating the expression level of p27 and p21 through ubiquitination and proteasomal degradation. SKP2-mediated loss of p27Kip1 is associated with poor clinical outcome in various types of cancers including hematological malignancies. It is however well established that SKP2 is an oncogene, and its targeting may be an attractive therapeutic strategy for the management of hematological malignancies...
August 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28767675/large-scale-identification-of-gossypium-hirsutum-genes-associated-with-verticillium-dahliae-by-comparative-transcriptomic-and-reverse-genetics-analysis
#2
Wenwei Zhang, Huachong Zhang, Kai Liu, Guiliang Jian, Fangjun Qi, Ning Si
Verticillium wilt is a devastating disease of cotton, which is caused by the soil-borne fungus Verticillium dahliae (V. dahliae). Although previous studies have identified some genes or biological processes involved in the interaction between cotton and V. dahliae, its underlying molecular mechanism remains unclear, especially in G. hirsutum. In the present study, we obtained an overview of transcriptome characteristics of resistant upland cotton (G. hirsutum) after V. dahliae infection at 24 h post-inoculation (hpi) via a high-throughput RNA-sequencing technique...
2017: PloS One
https://www.readbyqxmd.com/read/28743755/ubiquitination-of-exposed-glycoproteins-by-scf-fbxo27-directs-damaged-lysosomes-for-autophagy
#3
Yukiko Yoshida, Sayaka Yasuda, Toshiharu Fujita, Maho Hamasaki, Arisa Murakami, Junko Kawawaki, Kazuhiro Iwai, Yasushi Saeki, Tamotsu Yoshimori, Noriyuki Matsuda, Keiji Tanaka
Ubiquitination functions as a signal to recruit autophagic machinery to damaged organelles and induce their clearance. Here, we report the characterization of FBXO27, a glycoprotein-specific F-box protein that is part of the SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex, and demonstrate that SCF(FBXO27) ubiquitinates glycoproteins in damaged lysosomes to regulate autophagic machinery recruitment. Unlike F-box proteins in other SCF complexes, FBXO27 is subject to N-myristoylation, which localizes it to membranes, allowing it to accumulate rapidly around damaged lysosomes...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28736168/light-dependent-degradation-of-pif3-by-scf-ebf1-2-promotes-a-photomorphogenic-response-in-arabidopsis
#4
Jie Dong, Weimin Ni, Renbo Yu, Xing Wang Deng, Haodong Chen, Ning Wei
Plant seedlings emerging from darkness into the light environment undergo photomorphogenesis, which enables autotrophic growth with optimized morphology and physiology. During this transition, plants must rapidly remove photomorphogenic repressors accumulated in the dark. Among them is PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), a key transcription factor promoting hypocotyl growth. Here we report that, in response to light activation of phytochrome photoreceptors, EIN3-BINDING F BOX PROTEINs (EBFs) 1 and 2 mediate PIF3 protein degradation in a manner dependent on light-induced phosphorylation of PIF3...
July 18, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28722108/the-ubiquitin-ligase-scf-fbxw7%C3%AE-promotes-ata3-degradation
#5
Nan Song, Cheng Cao, Yiman Tang, Liyuan Bi, Yong Jiang, Yongsheng Zhou, Xin Song, Ling Liu, Wenshu Ge
GATA3 is a key transcription factor in cell fate determination and its dysregulation has been implicated in various types of malignancies. However, how the abundance and function of GATA3 are regulated remains unclear. Here, we report that GATA3 is physically associated with FBXW7α, and FBXW7α destabilizes GATA3 through assembly of a SKP1-CUL1-F-box E3 ligase complex. Importantly, we showed that FBXW7α promotes GATA3 ubiquitination and degradation in a GSK3 dependent manner. Furthermore, we demonstrated that FBXW7α inhibits breast cancer cells survival through destabilizing GATA3, and the expression level of FBXW7αis negatively correlated with that of GATA3 in breast cancer samples...
July 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28690630/lack-of-s-rnase-based-gametophytic-self-incompatibility-in-orchids-suggests-that-this-system-evolved-after-the-monocot-eudicot-split
#6
Shan-Ce Niu, Jie Huang, Yong-Qiang Zhang, Pei-Xing Li, Guo-Qiang Zhang, Qing Xu, Li-Jun Chen, Jie-Yu Wang, Yi-Bo Luo, Zhong-Jian Liu
Self-incompatibility (SI) is found in approximately 40% of flowering plant species and at least 100 families. Although orchids belong to the largest angiosperm family, only 10% of orchid species present SI and have gametophytic SI (GSI). Furthermore, a majority (72%) of Dendrobium species, which constitute one of the largest Orchidaceae genera, show SI and have GSI. However, nothing is known about the molecular mechanism of GSI. The S-determinants of GSI have been well characterized at the molecular level in Solanaceae, Rosaceae, and Plantaginaceae, which use an S-ribonuclease (S-RNase)-based system...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28652210/cyclin-f-a-component-of-an-e3-ubiquitin-ligase-complex-with-roles-in-neurodegeneration-and-cancer
#7
Jasmin Galper, Stephanie L Rayner, Alison L Hogan, Jennifer A Fifita, Albert Lee, Roger S Chung, Ian P Blair, Shu Yang
Cyclin F, encoded by CCNF, is the substrate recognition component of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCF(cyclin F). E3 ubiquitin ligases play a key role in ubiquitin-proteasome mediated protein degradation, an essential component of protein homeostatic mechanisms within the cell. By recognising and regulating the availability of several protein substrates, SCF(cyclin F) plays a role in regulating various cellular processes including replication and repair of DNA and cell cycle checkpoint control...
August 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28619822/cop9-signalosome-subunits-protect-capicua-from-mapk-dependent-and-independent-mechanisms-of-degradation
#8
Annabelle Suisse, DanQing He, Kevin Legent, Jessica E Treisman
The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here, we show that mutations in the Drosophila COP9 signalosome subunit 1b (CSN1b) gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of CSN1b mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes. It does so by protecting Capicua, a transcriptional repressor of EGFR target genes, from EGFR pathway-dependent ubiquitylation by a Cullin 1/SKP1-related A/Archipelago E3 ligase and subsequent proteasomal degradation...
July 15, 2017: Development
https://www.readbyqxmd.com/read/28614300/pten-counteracts-fbxl2-to-promote-ip3r3-and-ca-2-mediated-apoptosis-limiting-tumour-growth
#9
Shafi Kuchay, Carlotta Giorgi, Daniele Simoneschi, Julia Pagan, Sonia Missiroli, Anita Saraf, Laurence Florens, Michael P Washburn, Ana Collazo-Lorduy, Mireia Castillo-Martin, Carlos Cordon-Cardo, Said M Sebti, Paolo Pinton, Michele Pagano
In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the 'quasisynaptical' feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca(2+) release results in mitochondrial Ca(2+) overload and consequent apoptosis. Among the three mammalian IP3Rs, IP3R3 appears to be the major player in Ca(2+)-dependent apoptosis. Here we show that the F-box protein FBXL2 (the receptor subunit of one of 69 human SCF (SKP1, CUL1, F-box protein) ubiquitin ligase complexes) binds IP3R3 and targets it for ubiquitin-, p97- and proteasome-mediated degradation to limit Ca(2+) influx into mitochondria...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28609481/the-ubiquitin-conjugating-enzyme-cdc34-is-essential-for-cytokinesis-in-contrast-to-putative-subunits-of-a-scf-complex-in-trypanosoma-brucei
#10
Federico Rojas, Joanna Koszela, Jacqueline Búa, Briardo Llorente, Richard Burchmore, Manfred Auer, Jeremy C Mottram, María Teresa Téllez-Iñón
The ubiquitin-proteasome system is a post-translational regulatory pathway for controlling protein stability and activity that underlies many fundamental cellular processes, including cell cycle progression. Target proteins are tagged with ubiquitin molecules through the action of an enzymatic cascade composed of E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, and E3 ubiquitin ligases. One of the E3 ligases known to be responsible for the ubiquitination of cell cycle regulators in eukaryotes is the SKP1-CUL1-F-box complex (SCFC)...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28515316/dna-damage-induced-degradation-of-exo1-exonuclease-limits-dna-end-resection-to-ensure-accurate-dna-repair
#11
Nozomi Tomimatsu, Bipasha Mukherjee, Janelle Louise Harris, Francesca Ludovica Boffo, Molly Catherine 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 (ataxia telangiectasia-mutated) and ATR (ATM and Rad3-related) and by the cyclin-dependent kinases 1 and 2. After activation, EXO1 must also be restrained to prevent over-resection that is known to hamper optimal HR and trigger global genomic instability...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28506875/deubiquitinase-usp33-is-negatively-regulated-by-%C3%AE-trcp-through-ubiquitin-dependent-proteolysis
#12
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...
July 1, 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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