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Ying Feng, Ming-Yue Jin, Dong-Wei Liu, Li Wei
Mesangial cells played a central role in the pathophysiology of diabetic nephropathy (DN). Our goal was to evaluate the molecular mechanism that regulates loss of BMP7 protein expression in DN. The mRNA and protein levels of BMP7 or UBE4A were detected using qRT-PCR and Western blot respectively. Mass spectrometry and co-immunoprecipitation were used to explore the E3 ligase which regulated BMP7 post-translationally. We initially confirmed that BMP7 protein, but not mRNA, is downregulated when cultured under high glucose mimicking DN conditions, which was rescued by MG-132 treatment...
January 19, 2019: Archives of Physiology and Biochemistry
Keren Baranes-Bachar, Adva Levy-Barda, Judith Oehler, Dylan A Reid, Isabel Soria-Bretones, Ty C Voss, Dudley Chung, Yoon Park, Chao Liu, Jong-Bok Yoon, Wei Li, Graham Dellaire, Tom Misteli, Pablo Huertas, Eli Rothenberg, Kristijan Ramadan, Yael Ziv, Yosef Shiloh
Double-strand breaks (DSBs) are critical DNA lesions that robustly activate the elaborate DNA damage response (DDR) network. We identified a critical player in DDR fine-tuning: the E3/E4 ubiquitin ligase UBE4A. UBE4A's recruitment to sites of DNA damage is dependent on primary E3 ligases in the DDR and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites...
March 1, 2018: Molecular Cell
Ming-Peng Zhang, Wei-San Zhang, Jin Tan, Ming-Hui Zhao, Lin-Juan Lian, Jie Cai
Thyroid cancer patients with high miR-490-3p inhibit translation of PCBP1 mRNA, whereas in patients with low miR-490-3p PCBP1 mRNA expression is high; however, the resultant protein is targeted for degradation through the proteasome. The objective of the present study was to evaluate the molecular mechanism that regulates post-translation degradation of poly r(C) binding protein (PCBP) 1 expression in thyroid cancer cells. Mass spectrometric analysis of PCBP1 immunoprecipitates from MG-132 treated TPC1 cells revealed a list of ubiquitin ligases associated with PCBP1...
October 31, 2017: Bioscience Reports
Yanan Sun, Xiaopeng Jia, Qiang Gao, Xing Liu, Lianguo Hou
Epithelial to mesenchymal transition (EMT) is an important prerequisite for metastasis to secondary organs. Interleukin-like EMT inducer (ILEI) protein has been shown to translationally upregulated during EMT and metastatic progression as a consequence of aberrant TGF-β signaling. Our initial evaluation of FAM3C (encoding ILEI) and ILEI expression in normal prostate (PCS-440-010) and prostate cancer cell lines (DU145, LNCaP, and PC3) revealed detectable protein expression in only LNCaP cell line even though all cell lines tested had comparable FAM3C expression...
January 2017: IUBMB Life
S Anazi, S Maddirevula, E Faqeih, H Alsedairy, F Alzahrani, H E Shamseldin, N Patel, M Hashem, N Ibrahim, F Abdulwahab, N Ewida, H S Alsaif, H Al Sharif, W Alamoudi, A Kentab, F A Bashiri, M Alnaser, A H AlWadei, M Alfadhel, W Eyaid, A Hashem, A Al Asmari, M M Saleh, A AlSaman, K A Alhasan, M Alsughayir, M Al Shammari, A Mahmoud, Z N Al-Hassnan, M Al-Husain, R Osama Khalil, N Abd El Meguid, A Masri, R Ali, T Ben-Omran, P El Fishway, A Hashish, A Ercan Sencicek, M State, A M Alazami, M A Salih, N Altassan, S T Arold, M Abouelhoda, S M Wakil, D Monies, R Shaheen, F S Alkuraya
Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196)...
April 2017: Molecular Psychiatry
Raman Bansal, Priyanka Mittapelly, Yuting Chen, Praveen Mamidala, Chaoyang Zhao, Andy Michel
The brown marmorated stink bug (Halyomorpha halys) has emerged as one of the most important invasive insect pests in the United States. Functional genomics in H. halys remains unexplored as molecular resources in this insect have recently been developed. To facilitate functional genomics research, we evaluated ten common insect housekeeping genes (RPS26, EF1A, FAU, UBE4A, ARL2, ARP8, GUS, TBP, TIF6 and RPL9) for their stability across various treatments in H. halys. Our treatments included two biotic factors (tissues and developmental stages) and two stress treatments (RNAi injection and starvation)...
2016: PloS One
Cécile Naudin, Audrey Sirvent, Cédric Leroy, Romain Larive, Valérie Simon, Julie Pannequin, Jean-François Bourgaux, Josiane Pierre, Bruno Robert, Frédéric Hollande, Serge Roche
The adaptor SLAP is a negative regulator of receptor signalling in immune cells but its role in human cancer is ill defined. Here we report that SLAP is abundantly expressed in healthy epithelial intestine but strongly downregulated in 50% of colorectal cancer. SLAP overexpression suppresses cell tumorigenicity and invasiveness while SLAP silencing enhances these transforming properties. Mechanistically, SLAP controls SRC/EPHA2/AKT signalling via destabilization of the SRC substrate and receptor tyrosine kinase EPHA2...
2014: Nature Communications
Claus Meyer, Eric Kowarz, Sze-Fai Yip, Thomas Shek-Kong Wan, Tai-Kwong Chan, Theo Dingermann, Li-Chong Chan, Rolf Marschalek
Chromosomal rearrangements of the MLL gene are uncommon in myelodysplastic syndromes (MDSs), and few studies of their molecular structures and oncogenic mechanisms exist. Here, we present a case of de novo MDS with a normal karyotype at initial diagnosis and a mild clinical course. Five years after the initial diagnosis, investigators identified a complex rearrangement of the MLL gene without progression to acute leukemia. The 5' part of the MLL gene is fused out of frame with the LOC100131626 gene, and the 3' part of the MLL gene out of frame with the TCF12 gene...
October 2011: Cancer Genetics
Ignacio Marín
BACKGROUND: The patterns of emergence and diversification of the families of ubiquitin ligases provide insights about the evolution of the eukaryotic ubiquitination system. U-box ubiquitin ligases (UULs) are proteins characterized by containing a peculiar protein domain known as U box. In this study, the origin of the animal UUL genes is described. RESULTS: Phylogenetic and structural data indicate that six of the seven main UUL-encoding genes found in humans (UBE4A, UBE4B, UIP5, PRP19, CHIP and CYC4) were already present in the ancestor of all current metazoans and the seventh (WDSUB1) is found in placozoans, cnidarians and bilaterians...
October 27, 2010: BMC Evolutionary Biology
Xuhang Li, Laurie Conklin, Philip Alex
Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and characterization of new serological biomarkers (identified since 2007). These include five new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibodies against chemically synthesized (Sigma) two major oligomannose epitopes, Man alpha-1,3 Man alpha-1,2 Man (SigmaMan3) and Man alpha-1,3 Man alpha-1,2 Man alpha-1,2 Man (SigmaMan4)...
September 7, 2008: World Journal of Gastroenterology: WJG
Toshio Sakiyama, Hiroshi Fujita, Hirohito Tsubouchi
BACKGROUND: Identification of a disease- and organ-specific autoantigen can potentially contribute to understanding molecular mechanisms involved in Crohn's disease (CD) and lead to development of clinically useful markers. The aim was to identify potential intestinal autoantigens specific to patients with CD and evaluate their diagnostic value. METHODS: A cDNA expression library from normal terminal ileum was created and screened with pooled sera from 3 randomly selected patients with CD...
March 2008: Inflammatory Bowel Diseases
Ying Yang, Jian-qing Hou, Lu-yun Qu, Gui-qing Wang, Hong-wei Ju, Zhi-wei Zhao, Zhen-hai Yu, Hui-jun Yang
AIM: The differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues was investigated. METHODS: Restriction fragment differential display polymerase chain reaction (RFDD-PCR), semi-quantitative RT-PCR and immunohistochemical staining were applied to analyze the differentially expressed genes and proteins of ubiquitin specific proteases (USPs), USP2 and USP14, and ubiquitin factor E4A (UBE4A) between ovarian serous cystadenocarcinoma and adjacent normal tissues obtained from 40 patients aged from 29 to 72 years old, collected in 2005 year at excision of surgical operation with ovarian serous cystadenocarcinoma...
June 2007: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
G Vazquez-Ortiz, J A García, C J Ciudad, V Noé, S Peñuelas, R López-Romero, P Mendoza-Lorenzo, P Piña-Sánchez, M Salcedo
Cervical carcinoma (CC) is one of the most common cancers among women worldwide and the first cause of death among the Mexican female population. Human papillomavirus (HPV) infection is the most important etiologic factor for CC. Of the oncogenic types, HPV16 and HPV18 are found in 60-70% of invasive CCs worldwide. HPV18 appears to be associated with a more aggressive form of cervical neoplasia than HPV16 infection. At present, there are no studies on differentially expressed cellular genes between transformed cells harboring HPV16 and HPV18 sequences...
March 2007: International Journal of Gynecological Cancer
H Carén, A Holmstrand, R-M Sjöberg, T Martinsson
Chromosomes 11q and 1p are commonly deleted in advanced-stage neuroblastomas and are therefore assumed to contain tumour suppressor genes involved in the development of this cancer. The two UFD2 yeast gene human homologues, UBE4A and UBE4B, involved in the ubiquitin/proteasome pathway, are located in 11q and 1p, respectively. UBE4B has previously been analysed for mutations and one mutation in the splice donor site of exon 9, c.1439 + 1G > C, was found in a neuroblastoma tumour with fatal outcome. We speculated that the homologue UBE4A might be involved in an alternative tumourigenesis pathway...
February 2006: European Journal of Cancer
Gianmarco Contino, Francesca Amati, Sabina Pucci, Eugenio Pontieri, Flavia Pichiorri, Antonio Novelli, Annalisa Botta, Ruggiero Mango, Anna Maria Nardone, Federica Carla Sangiuolo, Gennaro Citro, Luigi Giusto Spagnoli, Giuseppe Novelli
The Ubiquitination Factor E4A gene (UBE4A) encodes for a U-box-type ubiquitin ligase, originally described as an E4 ubiquitination factor. UBE4A is a mammalian homolog of Saccharomyces cerevisiae Ufd2. The UBE4A gene has been mapped on the human chromosome region 11q23.3, a critical region involved in some specific cancers such as neuroblastoma. Northern blots analysis on foetal and adult human tissues revealed a single band of approximately 7.5 kb transcript most abundant in the heart, skeletal muscle and kidney...
March 17, 2004: Gene
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