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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
#1
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/29149301/use-of-domain-swapping-to-identify-candidate-amino-acids-involved-in-differential-interactions-between-two-allelic-variants-of-type-1%C3%A2-s-locus-f-box-protein-and-s3-rnase-in-petunia-inflata
#2
Lihua Wu, Justin S Williams, Ning Wang, Wasi A Khatri, Daniele San Román, Teh-Hui Kao
Petunia inflata possesses a self-incompatibility (SI) mechanism, which involves S-RNase and multiple S-locus F-box (SLF) genes at the polymorphic S-locus. For a given S-haplotype, each SLF is thought to interact with some of its non-self S-RNases, but not with its self-S-RNase. In this work, we studied an allelic pair of SLF1, S2-SLF1 and S3-SLF1, which differ in 44 amino acids and show differential interactions with S3-RNase. We first used an in vivo transgenic assay to determine whether four chimeric proteins of S2-SLF1 and S3-SLF1, each with one of the three functional domains swapped, interact with S3-RNase...
November 15, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29142209/fbxo4-mediated-degradation-of-fxr1-suppresses-tumorigenesis-in-head-and-neck-squamous-cell-carcinoma
#3
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/29137415/ubiquitin-conjugating-enzyme-e2-l3-promoted-tumor-growth-of-nsclc-through-accelerating-p27kip1-ubiquitination-and-degradation
#4
Xingjie Ma, Junjie Zhao, Fan Yang, Haitao Liu, Weibo Qi
The molecular pathogenesis of human lung cancer has not been completely clarified. Here, we reported that UBE2L3, a member of the ubiquitin-conjugating enzymes (E2s), were overexpressed in non-small-cell lung cancer (NSCLC) tissues compared with the non-tumor tissues. High expression of UBE2L3 was correlated with advanced tumor stage and adverse outcomes. Knockdown of UBE2L3 inhibited NSCLC cell growth while ectopic expression of UBE2L3 promoted NSCLC cell growth in a cell cycle dependent manner. The results of subcutaneous tumor xenograft studies revealed that knockdown of UBE2L3 attenuated the in vivo tumor growth...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134665/mechanistic-contributions-of-fbxo7-to-parkinson-s-disease
#5
REVIEW
Sabitha Joseph, Jörg Bernhard Schulz, Judith Stegmüller
Parkinson's disease (PD) is, without doubt, a burden on modern society as the prevalence increases significantly with age. Owing to this growing number of PD cases, it is more critical than ever to understand the pathogenic mechanisms underlying PD to identify therapeutic targets. The discovery of genetic mutations associated with PD and parkinsonism paves the way toward this goal. Even though, familial forms of the disease represent the minority of PD cases and some forms are so rare that there are only a few affected families, the research on the associated genes is invaluable...
November 14, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29125388/conserved-function-of-mediator-in-regulating-nuclear-hormone-receptor-activation-between-plants-and-animals
#6
Qingzhe Zhai, Lin Li, Chunpeng An, Chuanyou Li
Perception of the plant hormone jasmonoyl-isoleucine (JA-Ile) involves the formation of a co-receptor complex between COI1, the F-box subunit of a SCF-type E3 ubiquitin ligase, and its substrates, a group of jasmonate ZIM-domain (JAZ) transcriptional repressors. In recent studies, we show that MED25, a subunit of the Arabidopsis Mediator, physically and functionally interacts with COI1 and the master transcription factor MYC2 on MYC2 target promoters. Here we provide evidence that MED25 also physically interacts with a subset of JAZ proteins...
November 10, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29117943/fbxo31-suppresses-gastric-cancer-emt-by-targeting-snail1-for-proteasomal-degradation
#7
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/29114080/a-role-for-the-f-box-protein-hawaiian-skirt-in-plant-microrna-function
#8
Patricia L M Lang, Michael D Christie, Ezgi S Dogan, Rebecca Schwab, Jörg Hagmann, Anna-Lena Van de Weyer, Detlef Weigel, Emanuele Scacchi
As regulators of gene expression in multicellular organisms, microRNAs (miRNAs) are crucial for growth and development. While a plethora of factors involved in their biogenesis and action in Arabidopsis thaliana has been described, these processes and their fine-tuning are not fully understood. Here, we used plants expressing an artificial miRNA target mimic (MIM) to screen for negative regulators of miR156. We identified a new mutant allele of the F-box gene HAWAIIAN SKIRT (HWS; At3G61590), hws-5, as a suppressor of the MIM156-induced developmental and molecular phenotypes...
November 7, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29103612/composition-and-regulation-of-the-cellular-repertoire-of-scf-ubiquitin-ligases
#9
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...
October 26, 2017: Cell
https://www.readbyqxmd.com/read/29077002/the-role-of-mammalian-target-of-rapamycin-mtor-in-insulin-signaling
#10
REVIEW
Mee-Sup Yoon
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that controls a wide spectrum of cellular processes, including cell growth, differentiation, and metabolism. mTOR forms two distinct multiprotein complexes known as mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), which are characterized by the presence of raptor and rictor, respectively. mTOR controls insulin signaling by regulating several downstream components such as growth factor receptor-bound protein 10 (Grb10), insulin receptor substrate (IRS-1), F-box/WD repeat-containing protein 8 (Fbw8), and insulin like growth factor 1 receptor/insulin receptor (IGF-IR/IR)...
October 27, 2017: Nutrients
https://www.readbyqxmd.com/read/29072128/fbxw7-expression-affects-the-response-to-chemoradiotherapy-and-overall-survival-among-patients-with-oral-squamous-cell-carcinoma-a-single-center-retrospective-study
#11
Hidetaka Arita, Masashi Nagata, Ryoji Yoshida, Yuichiro Matsuoka, Akiyuki Hirosue, Kenta Kawahara, Junki Sakata, Hikaru Nakashima, Taku Kojima, Ryo Toya, Ryuji Murakami, Akimitsu Hiraki, Masanori Shinohara, Hideki Nakayama
FBXW7 (F-box and WD repeat domain containing-7) is a tumor suppressor protein that regulates the degradation of various oncoproteins in several malignancies. However, limited information is available regarding FBXW7 expression in oral squamous cell carcinoma. Therefore, this study aimed to determine the clinical significance of FBXW7 expression in oral squamous cell carcinoma. The FBXW7 expression patterns in oral squamous cell carcinoma and adjacent normal tissues from 15 patients who underwent radical resection were evaluated using quantitative real-time polymerase chain reaction and immunohistochemical staining...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29070679/the-e3-ubiquitin-ligase-scf-fbxl14-complex-stimulates-neuronal-differentiation-by-targeting-the-notch-signaling-factor-hes1-for-proteolysis
#12
Fangfang Chen, Chunxiao Zhang, Haonan Wu, Yue Ma, Xiaomin Luo, Xinqi Gong, Fan Jiang, Yaoting Gui, Hui Zhang, Fei Lu
Molecular oscillators are important cellular regulators of, for example, circadian clocks, oscillations of immune regulators, and short-period (ultradian) rhythms during embryonic development. The Notch signaling factor hairy and enhancer of split 1 (HES1) is a well-known repressor of proneural genes, and HES1 ultradian oscillation is essential for keeping cells in an efficiently proliferating progenitor state. HES1 oscillation is driven by both transcriptional self-repression and ubiquitin-dependent proteolysis...
October 25, 2017: Journal of Biological Chemistry
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/29048664/mir-25-promotes-metastasis-via-targeting-fbxw7-in-esophageal-squamous-cell-carcinoma
#14
Ye Hua, Kai Zhao, Gang Tao, Chunhua Dai, Yuting Su
Increasing evidence suggests that miR-25 can function as an oncogene in different types of human malignancies, whereas little is known concerning the role of miR-25 in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the role of miR-25 in ESCC and to determine the molecular mechanisms underlying its function. The expression level of miR-25 was detected in primary ESCC tissues and cell lines by real-time quantitative PCR. We also assessed whether knockdown of miR-25 influences in vitro cell invasion and migration...
September 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29040770/optimized-light-inducible-transcription-in-mammalian-cells-using-flavin-kelch-repeat-f-box1-gigantea-and-cry2-cib1
#15
Jose R Quejada, Seon-Hye E Park, Daniel W Awari, Fan Shi, Hannah E Yamamoto, Fuun Kawano, Juergen C Jung, Masayuki Yazawa
Light-inducible systems allow spatiotemporal control of a variety of biological activities. Here, we report newly optimized optogenetic tools to induce transcription with light in mammalian cells, using the Arabidopsis photoreceptor Flavin Kelch-repeat F-box 1 (FKF1) and its binding partner GIGANTEA (GI) as well as CRY2/CIB1. By combining the mutagenesis of FKF1 with the optimization of a split FKF1/GI dimerized Gal4-VP16 transcriptional system, we identified constructs enabling significantly improved light-triggered transcriptional induction...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040381/the-cug-translated-wt1-not-aug-wt1-is-an-oncogene
#16
Kun Yeong Lee, Young Jin Jeon, Hong Gyum Kim, Joohyun Ryu, Do Young Lim, Sung Keun Jung, Dong Hoon Yu, Hanyong Chen, Ann M Bode, Zigang Dong
The Wilms' tumor 1 (WT1) gene is believed to act as a canonical tumor suppressor. However, it has also been reported to function as an oncogene. Germline WT1 deletion is associated with Wilms' tumor and exogenous WT1 cDNA introduction into cells induces the transcriptional suppression of its oncogenic target genes. In contrast, high WT1 expression is associated with poor prognosis in patients with various cancers. Why WT1 acts as a tumor suppressor under certain conditions, but as an oncogene under other conditions is unknown...
October 10, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29036710/a-disulfide-bond-a-like-oxidoreductase-is-a-strong-candidate-gene-for-self-incompatibility-in-apricot-prunus-armeniaca-pollen
#17
Juan Vicente Muñoz-Sanz, Elena Zuriaga, María L Badenes, Carlos Romero
S-RNase based gametophytic self-incompatibility (SI) is a widespread prezygotic reproductive barrier in flowering plants. In the Solanaceae, Plantaginaceae and Rosaceae gametophytic SI is controlled by the pistil-specific S-RNases and the pollen S-locus F-box proteins but non-S-specific factors, namely modifiers, are also required. In apricot, Prunus armeniaca (Rosaceae), we previously mapped two pollen-part mutations that confer self-compatibility in cultivars Canino and Katy at the distal end of chromosome 3 (M-locus) unlinked to the S-locus...
September 25, 2017: Journal of Experimental Botany
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
#18
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/29018463/the-plant-immunity-regulating-f-box-protein-cpr1-supports-plastid-function-in-absence-of-pathogens
#19
Christiane Hedtmann, Wei Guo, Elena Reifschneider, Isabelle Heiber, Heiko Hiltscher, Jörn van Buer, Aiko Barsch, Karsten Niehaus, Beth Rowan, Tobias Lortzing, Anke Steppuhn, Margarete Baier
The redox imbalanced 6 mutant (rimb6) of Arabidopsis thaliana was isolated in a genetic screening approach for mutants with defects in chloroplast-to-nucleus redox signaling. It has an atypically low activation status of the 2-Cys peroxiredoxin-A promoter in the seedling stage. rimb6 shows wildtype-like germination, seedling development and greening, but slower growth and reduced biomass in the rosette stage. Mapping of the casual mutation revealed that rimb6 carries a single nucleotide polymorphism in the gene encoding CONSTITUTIVE EXPRESSER OF PATHOGENESIS RELATED (PR) GENES 1, CPR1 (At4g12560), leading to a premature stop codon...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29016933/rice-inositol-polyphosphate-kinase-osipk2-directly-interacts-with-osiaa11-to-regulate-lateral-root-formation
#20
Yao Chen, Qiaofeng Yang, Sihong Sang, Zhaoyun Wei, Peng Wang
The plant hormone auxin controls many aspects of plant growth and development by promoting the degradation of Auxin/Indole-3-acetic acid (Aux/IAA) proteins. The domain II (DII) of Aux/IAA proteins is sufficient for eliciting the degradation by directly interacting with the auxin receptor F-box protein TIR1 to form a TIR1/AFBs-Aux/IAA complex in an auxin-dependent manner. However, the underlying mechanisms of fine-tuning Aux/IAA degradation by auxin stimuli remain to be elucidated. Here, we show that OsIPK2, a rice (Oryza sativa) inositol polyphosphate kinase, directly interacts with an Aux/IAA protein OsIAA11 to repress its degradation...
November 1, 2017: Plant & Cell Physiology
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