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  • Open Access

    ARTICLE

    Isolation and characterization of β-transducin repeat-containing protein ligands screened using a high-throughput screening system

    XINTONG LIU1,2,3, EMIKO SANADA1,3,4, JIANG LI5, XIAOMENG LI6, HIROYUKI OSADA1,4,7,*, NOBUMOTO WATANABE1,2,3,*

    Oncology Research, Vol.31, No.5, pp. 645-654, 2023, DOI:10.32604/or.2023.030240

    Abstract β-transducin repeat-containing protein (β-TrCP) is an F-box protein subunit of the E3 Skp1-Cullin-F box (SCF) type ubiquitin-ligase complex, and provides the substrate specificity for the ligase. To find potent ligands of β-TrCP useful for the proteolysis targeting chimera (PROTAC) system using β-TrCP in the future, we developed a high-throughput screening system for small molecule β-TrCP ligands. We screened the chemical library utilizing the system and obtained several hit compounds. The effects of the hit compounds on in vitro ubiquitination activity of SCFβ-TrCP1 and on downstream signaling pathways were examined. Hit compounds NPD5943, NPL62020-01, and NPL42040-01 inhibited the TNFα-induced degradation of… More > Graphic Abstract

    Isolation and characterization of β-transducin repeat-containing protein ligands screened using a high-throughput screening system

  • Open Access

    ARTICLE

    Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer

    TING ZHOU1,#, PEIYING FU1,#, DONG CHEN2, RONGHUA LIU1,*

    Oncology Research, Vol.31, No.5, pp. 769-785, 2023, DOI:10.32604/or.2023.030166

    Abstract Late-stage ovarian cancer (OC) has a poor prognosis and a high metastasis rate, but the underlying molecular mechanism is unclear. RNA binding proteins (RBPs) play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis. In this study, we explored the molecular functions of a canonical RBP, Transformer 2β homolog (TRA2B), in cancer cells. TRA2B knockdown in HeLa cells and subsequent whole-transcriptome RNA sequencing (RNA-seq) analysis revealed the TRA2B-regulated alternative splicing (AS) profile. We disrupted TRA2B expression in epithelial OC cells and performed a series of experiments to confirm the resulting effects on OC cell proliferation, apoptosis… More >

  • Open Access

    REVIEW

    Scaffold proteins of cancer signaling networks: The paradigm of FK506 binding protein 51 (FKBP51) supporting tumor intrinsic properties and immune escape

    LAURA MARRONE1, MASSIMO D’AGOSTINO1, CAROLINA GIORDANO2, VALERIA DI GIACOMO1, SIMONA URZINI1, CHIARA MALASOMMA1, MARIA PAOLA GAMMELLA1, MARTINA TUFANO1, SIMONA ROMANO1,*, MARIA FIAMMETTA ROMANO1,*

    Oncology Research, Vol.31, No.4, pp. 423-436, 2023, DOI:10.32604/or.2023.028392

    Abstract Scaffold proteins are crucial regulators of signaling networks, and their abnormal expression may favor the development of tumors. Among the scaffold proteins, immunophilin covers a unique role as ‘protein-philin’ (Greek ‘philin’ = friend) that interacts with proteins to guide their proper assembly. The growing list of human syndromes associated with the immunophilin defect underscores the biological relevance of these proteins that are largely opportunistically exploited by cancer cells to support and enable the tumor’s intrinsic properties. Among the members of the immunophilin family, the FKBP5 gene was the only one identified to have a splicing variant. Cancer cells impose unique… More > Graphic Abstract

    Scaffold proteins of cancer signaling networks: The paradigm of FK506 binding protein 51 (FKBP51) supporting tumor intrinsic properties and immune escape

  • Open Access

    REVIEW

    Targeting the “undruggable” cancer driver genes: Ras, myc, and tp53

    XINGBO WU, DAN PAN, SHOUYI TANG, YINGQIANG SHEN*

    BIOCELL, Vol.47, No.7, pp. 1459-1472, 2023, DOI:10.32604/biocell.2023.028790

    Abstract The term “undruggable” is to describe molecules that are not targetable or at least hard to target pharmacologically. Unfortunately, some targets with potent oncogenic activity fall into this category, and currently little is known about how to solve this problem, which largely hampered drug research on human cancers. Ras, as one of the most common oncogenes, was previously considered “undruggable”, but in recent years, a few small molecules like Sotorasib (AMG-510) have emerged and proved their targeted anti-cancer effects. Further, myc, as one of the most studied oncogenes, and tp53, being the most common tumor suppressor genes, are both considered… More >

  • Open Access

    ARTICLE

    Hepatitis B virus X protein-mediated upregulation of miR-221 activates the CXCL12-CXCR4 axis to promote NKT cells in HBV-related hepatocellular carcinoma

    YUE CAO, LIN HU, YISHU TANG*

    BIOCELL, Vol.47, No.7, pp. 1537-1548, 2023, DOI:10.32604/biocell.2023.027205

    Abstract Backgrounds: Both hepatitis B virus X protein (HBx) and microRNA-221 (miR-221) have been implicated in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The present study demonstrates that HBx promotes HCC cell proliferation via the C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4 (CXCL12-CXCR4) axis. We predict that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC. Methods: After miR-221 mimic, miR-221 mimic negative control, miR-221 inhibitor, miR-221 inhibitor negative control were transfected into cells, the expression of CXCL12 and miR-221 was detected by qPCR and western blot. Then we constructed a stable HBV-HCC cell line.… More >

  • Open Access

    ARTICLE

    Zinc alpha 2 glycoprotein (ZAG): A potential novel pharmacological target in diabetic retinopathy

    UMAPATHY PRAKASH1, SUBRAMANIAM RAJESH BHARATHIDEVI1,*, RAMYA R. NADIG2, RAJIV RAMAN2, GIRISH SHIV RAO2, MUNA BHENDE2

    BIOCELL, Vol.47, No.7, pp. 1473-1482, 2023, DOI:10.32604/biocell.2023.027804

    Abstract Zinc alpha 2 glycoprotein (ZAG) is a 41 KDa secretory soluble glycoprotein found in different body fluids like the serum, saliva, sweat, breast milk, and urine. It is also found in tissues like the testis, epididymis, kidney, spleen, liver, lungs, heart, and brain. ZAG is an adipokine with multiple roles, including lipid mobilization, modulating glucose metabolisms, improving insulin sensitivity, inhibiting tumor proliferation through RNAse activity, and suppressing inflammation. Low levels of zinc and ZAG are linked to metabolic syndrome and are also reported as potential biomarkers for diabetic nephropathy. Interestingly zinc has been found to regulate the binding of ZAG… More >

  • Open Access

    ARTICLE

    A Novel Multi-Stage Bispectral Deep Learning Method for Protein Family Classification

    Amjed Al Fahoum*, Ala’a Zyout, Hiam Alquran, Isam Abu-Qasmieh

    CMC-Computers, Materials & Continua, Vol.76, No.1, pp. 1173-1193, 2023, DOI:10.32604/cmc.2023.038304

    Abstract Complex proteins are needed for many biological activities. Folding amino acid chains reveals their properties and functions. They support healthy tissue structure, physiology, and homeostasis. Precision medicine and treatments require quantitative protein identification and function. Despite technical advances and protein sequence data exploration, bioinformatics’ “basic structure” problem—the automatic deduction of a protein’s properties from its amino acid sequence—remains unsolved. Protein function inference from amino acid sequences is the main biological data challenge. This study analyzes whether raw sequencing can characterize biological facts. A massive corpus of protein sequences and the Globin-like superfamily’s related protein families generate a solid vector representation.… More >

  • Open Access

    Analysis of Subcellular Localization and Pathogenicity of Plum Bark Necrosis Stem-Pitting Associated Virus Protein P6

    Yuanyuan Li1,#, Jinze Mu2,#, Qingliang Li1, Huabing Liu3, Xuefeng Yuan2,*, Deya Wang1,*

    Phyton-International Journal of Experimental Botany, Vol.92, No.7, pp. 2079-2085, 2023, DOI:10.32604/phyton.2023.028237

    Abstract Infection of plum bark necrosis stem pitting associated virus (PBNSPaV) has been reported in many Prunus species in several countries, causing significant economic losses. The very small proteins encoded by plant viruses are often overlooked due to their short sequences and uncertain significance. However, numerous studies have indicated that they might play important roles in the pathogenesis of virus infection. The role of small hydrophobic protein P6, encoded by the open reading frame 2 of PBNSPaV, has not been well explored. In this study, we amplified the P6 fragment from a PBNSPaV isolate by RT-PCR using specific primers and found… More >

  • Open Access

    ARTICLE

    DDG1 and G Protein α Subunit RGA1 Interaction Regulates Plant Height and Senescence in Rice (Oryza sativa)

    Xi Liu1,2,#,*, Chuxuan Zhao2,#, Di Wang3,#, Gen Pan4, Xiaonan Ji2, Su Gao2, Tanxiao Du2, Yating Feng2, Wenjing Chen2

    Phyton-International Journal of Experimental Botany, Vol.92, No.7, pp. 2051-2064, 2023, DOI:10.32604/phyton.2023.028196

    Abstract Many studies have already shown that dwarfism and moderate delayed leaf senescence positively impact rice yield, but the underlying molecular mechanism of dwarfism and leaf senescence remains largely unknown. Here, using map-based cloning, we identified an allele of DEP2, DDG1, which controls plant height and leaf senescence in rice. The ddg1 mutant displayed dwarfism, short panicles, and delayed leaf senescence. Compared with the wild-type, ddg1 was insensitive to exogenous gibberellins (GA) and brassinolide (BR). DDG1 is expressed in various organs, especially in stems and panicles. Yeast two-hybrid assay, bimolecular fluorescent complementation and luciferase complementation image assay showed that DDG1 interacts… More >

  • Open Access

    ARTICLE

    Rice E3 Ligase-Like Protein OsPIAL1 Positively Regulated the Drought Stress Response but Negatively Regulated the Salt Stress Response

    Sang Ik Song*

    Phyton-International Journal of Experimental Botany, Vol.92, No.7, pp. 2017-2034, 2023, DOI:10.32604/phyton.2023.027469

    Abstract Small ubiquitin-like modifier (SUMO) E3 ligases that facilitate the conjugation of SUMO proteins to target substrates contain an SP-RING domain which is like the RING domain found in ubiquitin E3 ligases. In this study, we isolated and characterized the Oryza sativa protein inhibitor of activated STAT like1 (OsPIAL1) containing SP-RING domains, as the rice homolog of Arabidopsis PIALs. OsPIAL1 interacts with OsSUMO proteins but does not interact with rice SUMO-conjugating enzymes (OsSCEs). An analysis of transgenic rice plant shows that OsPIAL1 is involved in SUMO conjugation to SCEs but not in SUMO conjugation to substrates. In addition, this OsPIAL1 activity… More >

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