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Jiewen Zhang, Lijuan Kong, Sichao Guo, Mengmeng Bu, Qian Guo, Yuan Xiong, Ning Zhu, Chuan Qiu, Xuejing Yan, Qian Chen, Hongfei Zhang, Junling Zhuang, Qiong Wang, Samuel S Zhang, Yan Shen, Meihong Chen
Most of our knowledge about translation regulatory mechanisms comes from studies on lower organisms. However, the translation control system of higher organisms is less understood. Here we find that in 5' untranslated region (5'UTR) of human Annexin II receptor (AXIIR) mRNA, there are two upstream open reading frames (uORFs) acting in a fail-safe manner to inhibit the translation from the main AUG. These uORFs are unfavorable for re-initiation after termination of uORF translation. Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), hnRNPA0 and ELAV like RNA binding protein 1 (ELAVL1) bind to the 5'UTR of AXIIR mRNA...
October 26, 2016: Nucleic Acids Research
Łukasz Witek, Tomasz Janikowski, Piotr Bodzek, Anita Olejek, Urszula Mazurek
PURPOSE: Endometrial cancer is the most common gynecological malignancy in developed countries. The role of tumor suppressor genes (TSG) in endometrioid endometrial adenocarcinoma (EEC) has an important impact on patient survival prognosis. Thus, it is important to identify TSG transcripts that differentiate endometrial adenocarcinoma into various pathomorphological grades. The aim of this study was to analyze the expression profile of tumor suppressor genes related to the cell cycle in patients with endometrial adenocarcinoma across histological differentiation and to identify transcripts which differentiate endometrium into various pathomorphological grades...
September 2016: Advances in Medical Sciences
Ian G Cannell, Karl A Merrick, Sandra Morandell, Chang-Qi Zhu, Christian J Braun, Robert A Grant, Eleanor R Cameron, Ming-Sound Tsao, Michael T Hemann, Michael B Yaffe
In normal cells, p53 is activated by DNA damage checkpoint kinases to simultaneously control the G1/S and G2/M cell cycle checkpoints through transcriptional induction of p21(cip1) and Gadd45α. In p53-mutant tumors, cell cycle checkpoints are rewired, leading to dependency on the p38/MK2 pathway to survive DNA-damaging chemotherapy. Here we show that the RNA binding protein hnRNPA0 is the "successor" to p53 for checkpoint control. Like p53, hnRNPA0 is activated by a checkpoint kinase (MK2) and simultaneously controls both cell cycle checkpoints through distinct target mRNAs, but unlike p53, this is through the post-transcriptional stabilization of p27(Kip1) and Gadd45α mRNAs...
November 9, 2015: Cancer Cell
(no author information available yet)
The MK2/hnRNPA0 promotes the chemoresistance of TP53-deficient NSCLC tumors.
December 2015: Cancer Discovery
Chongjuan Wei, Bo Peng, Younghun Han, Wei V Chen, Joshua Rother, Gail E Tomlinson, C Richard Boland, Damien Chaussabel, Marsha L Frazier, Christopher I Amos
No abstract text is available yet for this article.
June 2015: Familial Cancer
Chongjuan Wei, Bo Peng, Younghun Han, Wei V Chen, Joshua Rother, Gail E Tomlinson, C Richard Boland, Damien Chaussabel, Marc Chaussabel, Marsha L Frazier, Christopher I Amos
We studied a large family that presented a strong familial susceptibility to multiple early onset cancers including prostate, breast, colon, and several other uncommon cancers. Through targeted gene, linkage, and whole genome sequencing analyses, we show that the presence of a variant in the regulatory region of HNRNPA0 associated with elevated cancer incidence in this family (Hazard ratio = 7.20, p = 0.0004). Whole genome sequencing identified a second rare protein changing mutation of WIF1 that interacted with the HNRNPA0 variant resulting in extremely high risk for cancer in carriers of mutations in both genes (p = 1...
June 2015: Familial Cancer
T M Darlington, R Pimentel, K Smith, A V Bakian, L Jerominski, J Cardon, N J Camp, W B Callor, T Grey, M Singleton, M Yandell, P F Renshaw, D A Yurgelun-Todd, D Gray, H Coon
Suicidal behavior is a complex disorder, with evidence for genetic risk independent of other genetic risk factors including psychiatric disorders. Since 1996, over 3000 DNA samples from Utah suicide decedents have been collected and banked for research use through the Utah Medical Examiner. In addition, over 12,000 Utah suicides were identified through examination of death certificates back to 1904. By linking this data with the Utah Population Database, we have identified multiple extended pedigrees with increased risk for suicide completion...
2014: Translational Psychiatry
David J Young, Angela Stoddart, Joy Nakitandwe, Shann-Ching Chen, Zhijian Qian, James R Downing, Michelle M Le Beau
The control of mRNA stability plays a central role in orchestrating gene-regulatory networks in hematopoietic cell growth, differentiation and tumorigenesis. HNRNPA0, which encodes an RNA-binding protein shown to regulate transcript stability via binding to the AU-rich elements of mRNAs, is located within the commonly deleted segment of 5q31.2 in myeloid neoplasms with a del(5q), and is expressed at haploinsufficient levels in these patients. We show that HNRNPA0 is normally highly expressed in hematopoietic stem cells and exhibits dynamic changes in expression during the course of differentiation...
June 2014: Haematologica
Susana Romero-Garcia, Heriberto Prado-Garcia, Jose Sullivan Lopez-Gonzalez
The ribonucleoproteins (hnRNPs) have important roles in multiple aspects of nucleic acid metabolism and in the regulation of different cellular processes. Abnormal expression of hnRNPs has been reported in several types of cancer including lung, pancreatic, and gastric carcinomas. Heterogenous tumor cell populations generate a tumor microenvironment that can present normoxic, hypoxic, or acidic regions. The analysis of hnRNP transcriptional responses considering the changing nature of the tumor microenvironment is important to understand tumor cell survival under stress conditions...
February 2014: Experimental Lung Research
Dimitar B Iliev, Ingrid Skjæveland, Jorunn B Jørgensen
BACKGROUND: Bacterial DNA is well-known for its potent immunostimulatory properties which have been attributed to the abundance of CpG dinucleotides within the genomes of prokaryotes. Research has found that mammalian TLR9 is a receptor which mediates the immune response to CpG DNA; however, its functional properties in non-mammalian vertebrates are still poorly characterized. Leukocytes isolated from lower vertebrates, including teleosts, respond to CpG DNA and TLR9 has been identified in many fish species; however, the ligand-binding properties of fish TLR9 have, so far, not been studied...
2013: BMC Immunology
H Christian Reinhardt, Pia Hasskamp, Ingolf Schmedding, Sandra Morandell, Marcel A T M van Vugt, Xiaozhe Wang, Rune Linding, Shao-En Ong, David Weaver, Steven A Carr, Michael B Yaffe
Following genotoxic stress, cells activate a complex kinase-based signaling network to arrest the cell cycle and initiate DNA repair. p53-defective tumor cells rewire their checkpoint response and become dependent on the p38/MK2 pathway for survival after DNA damage, despite a functional ATR-Chk1 pathway. We used functional genetics to dissect the contributions of Chk1 and MK2 to checkpoint control. We show that nuclear Chk1 activity is essential to establish a G(2)/M checkpoint, while cytoplasmic MK2 activity is critical for prolonged checkpoint maintenance through a process of posttranscriptional mRNA stabilization...
October 8, 2010: Molecular Cell
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