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promyelocytic leukemia protein

Mohamed Ali Maroui, Ghizlane Maarifi, Francis P McManus, Frederic Lamoliatte, Pierre Thibault, Mounira K Chelbi-Alix
We report that interferon (IFN) a treatment at short and long periods increases the global cellular SUMOylation and requires the presence of the SUMO E3 ligase promyelocytic leukemia protein (PML), the organizer of PML nuclear bodies (NBs). Several PML isoforms (PMLI-PMLVII) derived from a single PML gene by alternative splicing, share the same N-terminal region but differ in their C-terminal sequences. Introducing each of the human PML isoform in PML-negative cells revealed that enhanced SUMOylation in response to IFN is orchestrated by PMLIII and PMLIV...
March 13, 2018: Molecular & Cellular Proteomics: MCP
Fang Qiu, Changjiang Dong, Yanxin Liu, Xiaoqi Shao, Di Huang, Yanna Han, Bing Wang, Yanli Liu, Rong Huo, Petro Paulo, Zhiren Zhang, Dan Zhao, Wen-Feng Chu
BACKGROUND AND PURPOSE: Protein modification by small ubiquitin-like modifier (SUMO) plays a critical role in the pathogenesis of heart diseases. The present study was designed to determine whether ginkgolic acid (GA) as a SUMO-1 inhibitor exerts an inhibitory effect on cardiac fibrosis induced by myocardial infarction (MI). EXPERIMENTAL APPROACH: GA was delivered by osmotic pumps in MI mice. Masson staining, electron microscopy (EM) and echocardiography were used to assess cardiac fibrosis, ultrastructure and function...
March 7, 2018: Toxicology and Applied Pharmacology
Philipp E Merkl, Megan Orzalli, David M Knipe
The initial events after DNA virus infection involve a race between epigenetic silencing of the incoming viral DNA by host cell factors and expression of viral genes. Several host gene products, including the nuclear domain 10 (ND10) components PML (promyelocytic leukemia) and Daxx (death domain-associated protein 6), as well as IFI16 (interferon-inducible protein 16), have been shown to restrict herpes simplex virus 1 (HSV-1) replication. Whether IFI16 and ND10 components work together or separately to restrict HSV-1 replication is not known...
February 28, 2018: Journal of Virology
Rossella Avagliano Trezza, Janny van den Burg, Nico van den Oever, Ben Distel
Ubiquitination is a posttranslational protein modification that regulates most aspects of cellular life. The sheer number of ubiquitination enzymes that are present in a mammalian cell, over 700 in total, has thus far hampered the analysis of distinct protein ubiquitination cascades in a cellular context. To overcome this complexity we have developed a versatile vector system that allows the reconstitution of specific ubiquitination cascades in the model eukaryote Saccharomyces cerevisae (baker's yeast). The vector system consists of 32 modular yeast shuttle plasmids allowing inducible or constitutive expression of up to four proteins of interest in a single cell...
December 5, 2017: Microbial Cell
Paula Ana Iribarren, Lucía Ayelén Di Marzio, María Agustina Berazategui, Javier Gerardo De Gaudenzi, Vanina Eder Alvarez
SUMOylation is a post-translational modification conserved in eukaryotic organisms that involves the covalent attachment of the small ubiquitin-like protein SUMO to internal lysine residues in target proteins. This tag usually alters the interaction surface of the modified protein and can be translated into changes in its biological activity, stability or subcellular localization, among other possible outputs. SUMO can be attached as a single moiety or as SUMO polymers in case there are internal acceptor sites in SUMO itself...
2018: PloS One
Twishi Gulati, Cheng Huang, Franco Caramia, Dinesh Raghu, Piotr Jan Paul, Robert J A Goode, Simon Paul Keam, Scott G Williams, Sue Haupt, Oded Kleifeld, Ralf B Schittenhelm, Cristina Gamell, Ygal Haupt
Prostate cancer is a common cause of cancer-related death in men. E6AP (E6-Associated Protein), an E3 ubiquitin ligase and a transcription cofactor, is elevated in a subset of prostate cancer patients. Genetic manipulations of E6AP in prostate cancer cells expose a role of E6AP in promoting growth and survival of prostate cancer cells in vitro and in vivo. However, the effect of E6AP on prostate cancer cells is broad and it cannot be explained fully by previously identified tumour suppressor targets of E6AP, promyelocytic leukemia protein and p27...
February 20, 2018: Molecular & Cellular Proteomics: MCP
Jacob T Jackson, Ashley P Ng, Benjamin J Shields, Sue Haupt, Ygal Haupt, Matthew P McCormack
The hematopoietically expressed homeobox (Hhex) transcription factor is overexpressed in human myeloid leukemias. Conditional knockout models of murine acute myeloid leukemia indicate that Hhex maintains leukemia stem cell self-renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor suppressor locus, encoding p16 Ink4a and p19 Arf However, whether Hhex overexpression also affects hematopoietic differentiation is unknown. To study this, we retrovirally overexpressed Hhex in hematopoietic progenitors...
February 27, 2018: Blood Advances
Joanna Roszak, Anna Smok-Pieniążek, Maciej Stępnik
BACKGROUND: Arsenic trioxide (ATO) is a well-recognized antileukemic drug used for the treatment of newly diagnosed and relapsed acute promyelocytic leukemia (APL). A major drawback of therapy with ATO is the development of APL cell resistance, the mechanisms of which are still not clear. OBJECTIVES: The aim of this study was to investigate the role of the PI3K/Akt signaling pathway in ATOtreated human acute myeloid leukemia (HL-60) cells and in ATO-resistant clones...
December 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Wenjun Wu, Xiaoyan Han, Cai Wu, Guoqing Wei, Gaofeng Zheng, Yi Li, Yang Yang, Li Yang, Donghua He, Yi Zhao, Zhen Cai
Acute promyelocytic leukemia (APL) remains a challenge to cure due to the side effects of cytotoxic chemotherapy and drug resistance. The present study demonstrated that vernodalol, an active compound isolated from Centratherum anthelminticum, suppresses APL cell proliferation and induces cell cycle arrest in the G2/M phase through the upregulation of p21 and cell division cycle 25. In addition, vernodalol induced cellular apoptosis via the mitochondrial pathway as observed by the cleavage of caspase-9 as well as the release of cytochrome c and Smac/DIABLO into the cytosol...
February 2018: Oncology Letters
Shousheng Liu, Xiuyu Cai, Liangping Xia, Chang Jiang, Ping Chen, Xiaopai Wang, Bei Zhang, Hong Yun Zhao
Chloroquine (CQ) has been confirmed to exhibit antitumor effects on different types of cancer cell, but whether it exerts the same effect on acute promyelocytic leukemia (APL) cells remains to be confirmed. In the present study, the effects of various concentrations of CQ on the growth, apoptosis and cell cycle distribution of NB4 cells, as well as the potential mechanisms underlying these effects, were examined. The combined effect of CQ and arsenic trioxide (ATO) on the growth of NB4 cells was also determined...
February 2018: Oncology Letters
Myriam Koubi, Mathilde Poplineau, Julien Vernerey, Lia N'Guyen, Guillaume Tiberi, Sylvain Garciaz, Abdessamad El-Kaoutari, Muhammad A Maqbool, Jean-Christophe Andrau, Christel Guillouf, Andrew J Saurin, Estelle Duprez
The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes. Additionally, we identify a new association between PLZF and the histone methyltransferase, EZH2 at the genomic level...
February 7, 2018: Nucleic Acids Research
Kuo-Sheng Hsu, Hung-Ying Kao
Promyelocytic leukemia protein (PML) was originally identified as a fusion partner of retinoic acid receptor alpha in acute promyelocytic leukemia patients with the (15;17) chromosomal translocation, giving rise to PML-RARα and RARα-PML fusion proteins. A body of evidence indicated that PML possesses tumor suppressing activity by regulating apoptosis, cell cycle, senescence and DNA damage responses. PML is enriched in discrete nuclear substructures in mammalian cells with 0.2-1 μm diameter in size, referred to as alternately Kremer bodies, nuclear domain 10, PML oncogenic domains or PML nuclear bodies (NBs)...
2018: Cell & Bioscience
Jing Chen, Hulai Wei, Jie Cheng, Bei Xie, Bei Wang, Juan Yi, Baoying Tian, Zhuan Liu, Feifei Wang, Zhewen Zhang
The present study selected and characterized a multidrug-resistant HL-60 human acute promyelocytic leukemia cell line, HL-60/RS, by exposure to stepwise incremental doses of doxorubicin. The drug-resistant HL-60/RS cells exhibited 85.68-fold resistance to doxorubicin and were cross-resistant to other chemotherapeutics, including cisplatin, daunorubicin, cytarabine, vincristine and etoposide. The cells over-expressed the transporters P-glycoprotein, multidrug-resistance-related protein 1 and breast-cancer-resistance protein, encoded by the adenosine triphosphate-binding cassette (ABC)B1, ABCC1 and ABCG2 genes, respectively...
January 2018: Oncology Letters
Lu Liu, Liang Zhong, Yi Zhao, Min Chen, Shifei Yao, Lianwen Li, Chunlan Xiao, Zhiling Shan, Liugen Gan, Ting Xu, Beizhong Liu
Acute promyelocytic leukemia (APL), characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid α receptor (RARα) fusion protein, responds to treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, drug resistance and side effects restrict the application of these reagents. Hence, the development of novel therapeutic drugs for APL treatment is critical. Lapatinib, a small-molecule tyrosine kinase inhibitor, has been used in the treatment of different tumors. However, it is unclear whether lapatinib exerts antitumor effects on APL...
January 2018: Oncology Letters
P Binu, K Gifty, R C Vineetha, S Abhilash, P Arathi, R Harikumaran Nair
Arsenic trioxide is an effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. The clinical usefulness of arsenic trioxide is narrow due to different organ toxicities. It is hypothesized that the generation of reactive oxygen species by arsenic trioxide leads to thiol-based oxidative damage in rat myocardium. In this study, the defensive effect of eugenol on thiol-based oxidative stress was investigated in arsenic trioxide-treated rats. Rats were orally administered with arsenic trioxide (4 mg/kg per day) alone and in combination with eugenol (5 mg/kg per day) for 30 days...
January 26, 2018: Drug and Chemical Toxicology
Hui Shen, Ming Zhan, Yonglong Zhang, Shuai Huang, Sunwang Xu, Xince Huang, Min He, Yanhua Yao, Mohan Man, Jian Wang
Gallbladder cancer (GBC) is a malignant cancer with very poor prognosis. Although promyelocytic leukemia zinc-finger protein (PLZF) was reported to be deregulated in numerous cancers and also relevant to clinical prognosis, its role in GBC progression has been little known. In this study, we found PLZF expression was decreased in GBC, correlating to advanced TNM stage, distant metastasis, and shorter overall survival. Moreover, ectopic PLZF expression in GBC cells (NOZ and GBC-SD) significantly reduced the cell proliferation, migration, and invasion...
January 22, 2018: Cell Death & Disease
Yan Wang, Hai-Hong Sun, Ming-Hua Sui, Jun-Jie Ma
Acute promyelocytic leukemia (APL) is a subtype of acute myelocytic leukemia. Previous studies have reported a number of functions and therapeutic roles of microRNAs (miRs) in APL, and have suggested that miR-218 acts as a tumor suppressor in a number of types of human cancer; however, its role in APL remains unclear. In the present study, the expression of miR-218 and its effects on the viability and proliferation of HL-60 cells was investigated. Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that miR-218 was frequently downregulated in APL marrow tissues compared with normal marrow tissues...
December 2017: Oncology Letters
Kai-Ling Jiang, Liang Zhong, Xiao-Qun Yang, Peng-Peng Ma, Hui Wang, Xin-Yu Zhu, Bei-Zhong Liu
Acute promyelocytic leukemia (APL) is characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid receptor-α (RAR-α) fusion protein. PML-RARα can be cleaved by neutrophil elastase (NE) in several positions in cells in the promyelocytic stage, nuclear location signal (NLS)-negative PML and NLS-RARα may be the products of PML-RARα by NE. The function of NLS-RARα may be affected by the addition of NLS, which would alter its localization in cells, as the role of NLS is to identify proteins for transport to the nucleus...
December 2017: Oncology Letters
Koji Yamanegi, Naoko Yamada, Keiji Nakasho, Hiroshi Nishiura
Although C5a receptor (C5aR) interacting with its agonist C5a promotes acute inflammation during the initiation phase, the roles of the recycling C5aR during the resolution phase are still unclear. We found that C5aR interacted with its antagonist/agonist ribosomal protein S19 (RP S19) polymer or a RP S19 polymer functional analogue S-tagged C5a/RP S19, which connects an RP S19 C-terminus (IAGQVAAANKKH) to the S-tagged C5a C-terminus, promoted acute inflammation at the resolution phase via an activation of the apoptosis-inducing transcription factor delta lactoferrin (δLf) in neutrophils and the membrane mobilizing factor full-length annexin A3 (ANXA3) in macrophages...
December 29, 2017: Pathology International
Hideaki Ando, Katsuhiro Kawaai, Benjamin Bonneau, Katsuhiko Mikoshiba
The calcium ion (Ca2+) is a ubiquitous intracellular signaling molecule that regulates diverse physiological and pathological processes, including cancer. Increasing evidence indicates that oncogenes and tumor suppressors regulate the Ca2+ transport systems. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-activated Ca2+ release channels located on the endoplasmic reticulum (ER). They play pivotal roles in the regulation of cell death and survival by controlling Ca2+ transfer from the ER to mitochondria through mitochondria-associated ER membranes (MAMs)...
December 20, 2017: Advances in Biological Regulation
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