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https://www.readbyqxmd.com/read/29320569/transcriptome-profiling-of-pumpkin-cucurbita-moschata-duch-leaves-infected-with-powdery-mildew
#1
Wei-Li Guo, Bi-Hua Chen, Xue-Jin Chen, Yan-Yan Guo, He-Lian Yang, Xin-Zheng Li, Guang-Yin Wang
Cucurbit powdery mildew (PM) is one of the most severe fungal diseases, but the molecular mechanisms underlying PM resistance remain largely unknown, especially in pumpkin (Cucurbita moschata Duch.). The goal of this study was to identify gene expression differences in PM-treated plants (harvested at 24 h and 48 h after inoculation) and untreated (control) plants of inbred line "112-2" using RNA sequencing (RNA-Seq). The inbred line "112-2" has been purified over 8 consecutive generations of self-pollination and shows high resistance to PM...
2018: PloS One
https://www.readbyqxmd.com/read/29299176/f-box-proteins-in-epigenetic-regulation-of-cancer
#2
REVIEW
Jia Shen, Charles Spruck
Epigenetic abnormalities are now realized as important as genetic alterations in contributing to the initiation and progression of cancer. Recent advancements in the cancer epigenetics field have identified extensive alterations of the epigenetic network in human cancers, including histone modifications and DNA methylation. F-box proteins, the substrate receptors of SCF (SKP1-Cullin1-F-box protein) E3 ubiquitin ligases, can directly and indirectly affect the balance of epigenetic regulation. In this brief review, we discuss our current understanding of F-box proteins in cellular epigenetic regulation and how dysregulation of these processes contribute to cancer development...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29299126/hdac-inhibition-as-a-treatment-concept-to-combat-temsirolimus-resistant-bladder-cancer-cells
#3
Eva Juengel, Ramin Najafi, Jochen Rutz, Sebastian Maxeiner, Jasmina Makarevic, Frederik Roos, Igor Tsaur, Axel Haferkamp, Roman A Blaheta
Introduction: Although the mechanistic target of rapamycin (mTOR) might be a promising molecular target to treat advanced bladder cancer, resistance develops under chronic exposure to an mTOR inhibitor (everolimus, temsirolimus). Based on earlier studies, we proposed that histone deacetylase (HDAC) blockade might circumvent resistance and investigated whether HDAC inhibition has an impact on growth of bladder cancer cells with acquired resistance towards temsirolimus. Results: The HDAC inhibitor valproic acid (VPA) significantly inhibited growth, proliferation and caused G0/G1 phase arrest in RT112res and UMUC-3res...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29279382/structural-basis-of-the-phosphorylation-independent-recognition-of-cyclin-d1-by-the-scffbxo31-ubiquitin-ligase
#4
Yunfeng Li, Kai Jin, Eric Bunker, Xiaojuan Zhang, Xuemei Luo, Xuedong Liu, Bing Hao
Ubiquitin-dependent proteolysis of cyclin D1 is associated with normal and tumor cell proliferation and survival. The SCFFBXO31 (Skp1-Cul1-Rbx1-FBXO31) ubiquitin ligase complex mediates genotoxic stress-induced cyclin D1 degradation. Previous studies have suggested that cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm. Here we present the crystal structures of the Skp1-FBXO31 complex alone and bound to a phosphorylated cyclin D1 C-terminal peptide...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29251491/glycosylation-promotes-random-coil-to-helix-transition-in-a-region-of-a-protist-skp1-associated-with-f-box-binding
#5
Xianzhong Xu, Alexander Eletsky, M Osman Sheikh, James H Prestegard, Christopher M West
Cullin-Ring-Ligases mediate protein polyubiquitination, a signal for degradation in the 26S-proteasome. The CRL1 class consists of Skp1/cullin-1/F-box protein/Rbx1 (SCF) complexes that cyclically associate with ubiquitin-E2 to build the polyubiquitin chain. Within the SCF complex, the 162-amino acid DdSkp1 from Dictyostelium bridges cullin-1 with an F-box protein (FBP), the specificity factor for substrate selection. The hydroxylation-dependent glycosylation of Pro143 of DdSkp1 by a pentasaccharide forms the basis of a novel O2-sensing mechanism in the social amoeba Dictyostelium and other protists...
December 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/29212814/structural-basis-for-assembly-of-the-cbf3-kinetochore-complex
#6
Vera Leber, Andrea Nans, Martin R Singleton
Eukaryotic chromosomes contain a specialised region known as the centromere, which forms the platform for kinetochore assembly and microtubule attachment. The centromere is distinguished by the presence of nucleosomes containing the histone H3 variant, CENP-A. In budding yeast, centromere establishment begins with the recognition of a specific DNA sequence by the CBF3 complex. This in turn facilitates CENP-ACse4 nucleosome deposition and kinetochore assembly. Here, we describe a 3.6 Å single-particle cryo-EM reconstruction of the core CBF3 complex, incorporating the sequence-specific DNA-binding protein Cep3 together with regulatory subunits Ctf13 and Skp1...
December 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29192328/crispr-cas9-mediated-knockout-of-pissk1-reveals-essential-role-of-s-locus-f-box-protein-containing-scf-complexes-in-recognition-of-non-self-s-rnases-during-cross-compatible-pollination-in-self-incompatible-petunia-inflata
#7
Linhan Sun, Teh-Hui Kao
Function of Petunia PiSSK1. Self-incompatibility (SI), an inbreeding-preventing mechanism, is regulated in Petunia inflata by the polymorphic S-locus, which houses multiple pollen-specific S-locus F-box (SLF) genes and a single pistil-specific S-RNase gene. S 2-haplotype and S 3-haplotype possess the same 17 polymorphic SLF genes (named SLF1 to SLF17), and each SLF protein produced in pollen is assembled into an SCF (Skp1-Cullin1-F-box) E3 ubiquitin ligase complex. A complete suite of SLF proteins is thought to collectively interact with all non-self S-RNases to mediate their ubiquitination and degradation by the 26S proteasome, allowing cross-compatible pollination...
November 30, 2017: Plant Reproduction
https://www.readbyqxmd.com/read/29150959/nono-ubiquitination-is-mediated-by-fbw7-and-gsk3-%C3%AE-via-a-degron-lost-upon-chromosomal-rearrangement-in-cancer
#8
Luigi Alfano, Antonella Caporaso, Angela Altieri, Caterina Costa, Iris M Forte, Carmelina A Iannuzzi, Daniela Barone, Luca Esposito, Antonio Giordano, Francesca Pentimalli
NONO is an RNA-binding protein involved in transcription, mRNA splicing, DNA repair and checkpoint activation in response to UV radiation. NONO expression has been found altered in several tumour types, including prostate, colon, breast, melanoma and in papillary renal carcinoma, in which an X chromosome inversion generates a NONO-TFE3 fusion protein. Upon such rearrangement, NONO loses its C-terminal domain. Through bioinformatics analysis, we identified a putative degron motif, known to be recognized by the Skp1-Cul1-F-box-protein (SCF) complex...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29142209/fbxo4-mediated-degradation-of-fxr1-suppresses-tumorigenesis-in-head-and-neck-squamous-cell-carcinoma
#9
Shuo Qie, Mrinmoyee Majumder, Katarzyna Mackiewicz, Breege V Howley, Yuri K Peterson, Philip H Howe, Viswanathan Palanisamy, J Alan Diehl
The Fbxo4 tumour suppressor is a component of an Skp1-Cul1-F-box E3 ligase for which two substrates are known. Here we show purification of SCF(Fbxo4) complexes results in the identification of fragile X protein family (FMRP, Fxr1 and Fxr2) as binding partners. Biochemical and functional analyses reveal that Fxr1 is a direct substrate of SCF(Fbxo4). Consistent with a substrate relationship, Fxr1 is overexpressed in Fbxo4 knockout cells, tissues and in human cancer cells, harbouring inactivating Fbxo4 mutations...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29117943/fbxo31-suppresses-gastric-cancer-emt-by-targeting-snail1-for-proteasomal-degradation
#10
Shuiyan Zou, Cunying Ma, Fenghua Yang, Xia Xu, Jihui Jia, Zhifang Liu
The F-box protein FBXO31, a component of the Skp1/Cul1/F-box (SCF) E3 ubiquitin ligase complex, plays an important regulatory role in neuronal development, stress response and tumorigenesis. Our recent report indicates that FBXO31 functions as a tumor suppressor in gastric cancer and the loss of FBXO31 protein is associated with a higher malignant phenotype and poorer prognosis. However, little is known about the underlying mechanism. In this study, FBXO31 inhibits gastric cancer progression by suppressing the epithelial-mesenchymal transition (EMT)...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29103612/composition-and-regulation-of-the-cellular-repertoire-of-scf-ubiquitin-ligases
#11
Justin M Reitsma, Xing Liu, Kurt M Reichermeier, Annie Moradian, Michael J Sweredoski, Sonja Hess, Raymond J Deshaies
SCF (Skp1-Cullin-F-box) ubiquitin ligases comprise several dozen modular enzymes that have diverse roles in biological regulation. SCF enzymes share a common catalytic core containing Cul1⋅Rbx1, which is directed toward different substrates by a variable substrate receptor (SR) module comprising 1 of 69 F-box proteins bound to Skp1. Despite the broad cellular impact of SCF enzymes, important questions remain about the architecture and regulation of the SCF repertoire, including whether SRs compete for Cul1 and, if so, how this competition is managed...
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29099417/cell-cycle-dependent-translocation-and-regulatory-mechanism-of-cacybp-sip-in-gastric-cancer-cells
#12
Yang Chen, Kun Zhang, Xiaosu Wang, Qiaoneng Li, Qingfeng Wu, Xiaoxuan Ning
Our previous results showed that calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP) inhibits the proliferation and tumorigenicity of gastric cancer; however, the exact mechanism remains unclear, especially from the aspect of cell cycle. The subcellular localization of CacyBP/SIP, Siah-1, and Skp1 in SGC7901 gastric cancer cells was assessed by immunofluorescence after cell cycle synchronization. Levels of CacyBP/SIP, Siah-1, Skp1, β-catenin, and p-ERK1/2 were analyzed by western blotting. CacyBP/SIP phosphorylation (p-CacyBP/SIP) and the combining capacity of Siah-1 and Skp1 with CacyBP/SIP in nucleoprotein were determined by immunoprecipitation...
November 2, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29050305/calyxin-y-sensitizes-cisplatin-sensitive-and-resistant-hepatocellular-carcinoma-cells-to-cisplatin-through-apoptotic-and-autophagic-cell-death-via-scf-%C3%AE-trcp-mediated-eef2k-degradation
#13
Chao Zhang, Jian-Li Lei, Hao Zhang, Yuan-Zheng Xia, Pei Yu, Lei Yang, Ling-Yi Kong
The down-regulation of eukaryotic elongation factor-2 kinase (eEF2K) is associated with an enhancement in the sensitivity of malignant cells to chemotherapeutic agents. In this study, we found that the silencing of eEF2K enhanced cisplatin (CDDP)-induced cytotoxicity in CDDP-sensitive (HepG2) and resistant (HepG2/CDDP) cells. Calyxin Y, a unique chalcone diarylheptanoid adduct, down-regulated eEF2K by promoting Skp1-Cul1-F-box protein (SCF) β-transducin repeat-containing protein (βTrCP)-mediated protein degradation and synergistically enhanced the cytotoxicity of CDDP...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29021214/casein-kinase-ii-phosphorylation-of-cyclin-f-at-serine-621-regulates-the-lys48-ubiquitylation-e3-ligase-activity-of-the-scf-cyclin-f-complex
#14
Albert Lee, Stephanie L Rayner, Alana De Luca, Serene S L Gwee, Marco Morsch, Vinod Sundaramoorthy, Hamideh Shahheydari, Audrey Ragagnin, Bingyang Shi, Shu Yang, Kelly L Williams, Emily K Don, Adam K Walker, Katharine Y Zhang, Justin J Yerbury, Nicholas J Cole, Julie D Atkin, Ian P Blair, Mark P Molloy, Roger S Chung
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that is characterized by progressive weakness, paralysis and muscle loss often resulting in patient death within 3-5 years of diagnosis. Recently, we identified disease-linked mutations in the CCNF gene, which encodes the cyclin F protein, in cohorts of patients with familial and sporadic ALS and frontotemporal dementia (FTD) (Williams KL et al 2016 Nat. Commun.7, 11253. (doi:10.1038/ncomms11253)). Cyclin F is a part of a Skp1-Cul-F-box (SCF) E3 ubiquitin-protein ligase complex and is responsible for ubiquitylating proteins for degradation by the proteasome...
October 2017: Open Biology
https://www.readbyqxmd.com/read/28985004/efficient-ask-assisted-system-for-expression-and-purification-of-plant-f-box-proteins
#15
Haiou Li, Ruifeng Yao, Sui Ma, Shuai Hu, Suhua Li, Yupei Wang, Chun Yan, Daoxin Xie, Jianbin Yan
Ubiquitin-mediated protein degradation plays an essential role in plant growth and development as well as responses to environmental and endogenous signals. F-box protein is one of the key components of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which recruit specific substrate proteins for subsequent ubiquitination and 26S proteasome-mediated degradation to regulate developmental processes and signaling networks. However, it is not easy to obtain purified F-box proteins with high activity due to their unstable protein structures...
September 5, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28970512/multiple-regulatory-mechanisms-of-the-biological-function-of-nrf3-nfe2l3-control-cancer-cell-proliferation
#16
A M Masudul Azad Chowdhury, Hiroki Katoh, Atsushi Hatanaka, Hiroko Iwanari, Nanami Nakamura, Takao Hamakubo, Tohru Natsume, Tsuyoshi Waku, Akira Kobayashi
Accumulated evidence suggests a physiological relationship between the transcription factor NRF3 (NFE2L3) and cancers. Under physiological conditions, NRF3 is repressed by its endoplasmic reticulum (ER) sequestration. In response to unidentified signals, NRF3 enters the nucleus and modulates gene expression. However, molecular mechanisms underlying the nuclear translocation of NRF3 and its target gene in cancer cells remain poorly understood. We herein report that multiple regulation of NRF3 activities controls cell proliferation...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28954236/the-e3%C3%A2-ubiquitin-ligase-scf-cyclin-f-transmits-akt-signaling-to-the-cell-cycle-machinery
#17
Rajarshi Choudhury, Thomas Bonacci, Xianxi Wang, Andrew Truong, Anthony Arceci, Yanqiong Zhang, Christine A Mills, Jennifer L Kernan, Pengda Liu, Michael J Emanuele
The oncogenic AKT kinase is a key regulator of apoptosis, cell growth, and cell-cycle progression. Despite its important role in proliferation, it remains largely unknown how AKT is mechanistically linked to the cell cycle. We show here that cyclin F, a substrate receptor F-box protein for the SCF (Skp1/Cul1/F-box) family of E3 ubiquitin ligases, is a bona fide AKT substrate. Cyclin F expression oscillates throughout the cell cycle, a rare feature among the 69 human F-box proteins, and all of its known substrates are involved in proliferation...
September 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/28952040/rational-redesign-of-a-cation%C3%A2-%C3%A2-%C3%A2-%C3%AF-%C3%A2-%C3%A2-%C3%A2-%C3%AF-stacking-at-cardiovascular-fbw7-skp1-complex-interface-and-its-application-for-deriving-self-inhibitory-peptides-to-disrupt-the-complex-interaction
#18
Jing Zhou, Yao-Sheng Wang
The Fbw7-Skp1 complex is an essential component in the formation and development of the mammalian cardiovascular system; the complex interaction is mediated through binding of Skp1 C-terminal peptide (qGlu-peptide) to the F-box domain of Fbw7. By visually examining the crystal structure, we identified a typical cation ···π···π stacking system at the complex interface, which is formed by the Trp1159 residue of qGlu-peptide with the Lys2299 and His2359 residues of Fbw7 F-box domain. Both hybrid quantum mechanics/molecular mechanics (QM/MM) analysis of the real domain-peptide complex and electron-correlation ab initio calculation of the stacking system model suggested that the cation···π···π plays an important role in stabilizing the complex; substitution of peptide Trp1159 residue with aromatic Phe and Tyr would not cause a considerable effect on the configuration and energetics of cation···π···π stacking system, whereas His substitution seems to largely destabilize the system...
September 26, 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28947420/skp2-mediated-stabilization-of-mth1-promotes-survival-of-melanoma-cells-upon-oxidative-stress
#19
Jia Yu Wang, Guang Zhi Liu, James S Wilmott, Ting La, Yu Chen Feng, Hamed Yari, Xu Guang Yan, Rick F Thorne, Richard A Scolyer, Xu Dong Zhang, Lei Jin
MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA, however, there is little understanding of how MTH1 itself is regulated. Here we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. While Skp2 along with other components of the Skp1-cullin-F-box (SCF) ubiquitin ligase complex were physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression...
September 25, 2017: Cancer Research
https://www.readbyqxmd.com/read/28939596/the-f-box-protein-zygo1-mediates-bouquet-formation-to-promote-homologous-pairing-synapsis-and-recombination-in-rice-meiosis
#20
Fanfan Zhang, Ding Tang, Yi Shen, Zhihui Xue, Wenqing Shi, Lijun Ren, Guijie Du, Yafei Li, Zhukuan Cheng
Telomere bouquet formation, a highly conserved meiotic event, plays an important role in homologous pairing and therefore progression of meiosis; however, the underlying molecular mechanism remains largely unknown. Here, we identified ZYGOTENE 1 (ZYGO1), a novel F-box protein in rice (Oryza sativa), and verified its essential role in bouquet formation during early meiosis. In zygo1 mutants, zygotene chromosome aggregation and telomere clustering failed to occur. The suppressed telomere clustering in homologous pairing aberration in rice meiosis 1 (pair1) zygo1 and rice completion of meiotic recombination (Oscom1) zygo1 double mutants, together with the altered localization of OsSAD1 (a SUN protein associated with the nuclear envelope) in zygo1 showed that ZYGO1 has a significant function in bouquet formation...
September 22, 2017: Plant Cell
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