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Namrata Gupta, Suhani Thakker, Subhash C Verma
The establishment of latency is an essential for lifelong persistence and pathogenesis of Kaposi's sarcoma-associated herpesvirus (KSHV). Latency-associated nuclear antigen (LANA) is the most abundantly expressed protein during latency and is important for viral genome replication and transcription. Replication-coupled nucleosome assembly is a major step in packaging the newly synthesized DNA into chromatin, but the mechanism of KSHV genome chromatinization post-replication is not understood. Here, we show that nucleosome assembly protein 1-like protein 1 (NAP1L1) associates with LANA...
2016: Scientific Reports
Fikret Gurkan Agircan, Shoji Hata, Carmen Nussbaum-Krammer, Enrico Atorino, Elmar Schiebel
Separase is a caspase-like cysteine protease that is best known for its essential role during the metaphase-to-anaphase transition when it cleaves the cohesin ring complex that keeps the sister chromatids together. Another important function of separase is to regulate the process of centriole separation, known as centriole disengagement, at the end of mitosis. We used proximity-dependent biotin identification (BioID) to expand our knowledge on the identity of separase's proximity interactors. We show that separase BioID labeled two domains at the mother centriole: an area underneath the centriolar appendages and another at the proximal end of the mother centriole...
September 16, 2016: Biochemical and Biophysical Research Communications
Yuan Yan, Peipei Yin, Hui Gong, Yuanyuan Xue, Guoping Zhang, Bo Fang, Zhidan Chen, Yang Li, Chunjie Yang, Zheyong Huang, Xiangdong Yang, Junbo Ge, Yunzeng Zou
BACKGROUND/AIMS: To investigate whether nucleosome assembly protein 1-like 1 (Nap1l1) regulates the proliferation of induced pluripotent stem cells (iPSC) and the potential mechanisms. METHODS: Nap1l1-knockdown-iPSC and Nap1l1-overexpression-iPSC were constructed by transfection of lentiviral particles. The proliferation of iPSC was detected by MTT analysis, and cell cycle was analyzed by flow cytometry. RESULTS: Nap1l1 overexpression promoted iPSC proliferation and induced G2/M transition compared to their control iPSC while Nap1l1-knockdown-iPSC dramatically displayed the reduced proliferation and accumulated G2/M phase cells...
2016: Cellular Physiology and Biochemistry
Simon Schimmack, Andrew Taylor, Ben Lawrence, Daniele Alaimo, Hubertus Schmitz-Winnenthal, Markus W Büchler, Irvin M Modlin, Mark Kidd
BACKGROUND: The chromatin remodeler NAP1L1, which is upregulated in small intestinal neuroendocrine neoplasms (NENs), has been implicated in cell cycle progression. As p57(Kip2) (CDKN1C), a negative regulator of proliferation and a tumor suppressor, is controlled by members of the NAP1 family, we tested the hypothesis that NAP1L1 may have a mechanistic role in regulating pancreatic NEN proliferation through regulation of p57(Kip2). RESULTS: NAP1L1 silencing (siRNA and shRNA/lipofectamine approach) decreased proliferation through inhibition of mechanistic (mammalian) target of rapamycin pathway proteins and their phosphorylation (p < 0...
2014: Epigenetics & Chromatin
Nobuya Takahashi, Yasukazu Hozumi, Toshiaki Tanaka, Masashi Okada, Ken Iseki, Kiyoshi Hayasaka, Kaoru Goto
Diacylglycerol kinase (DGK) catalyzes conversion of a lipid second messenger diacylglycerol to another messenger molecule phosphatidic acid. Consequently, DGK plays a pivotal role in cellular pathophysiology by regulating the levels of these two messengers. We reported previously that DGKζ translocates from the nucleus to cytoplasm in hippocampal neurons under ischemic/hypoxic stress. In addition, we also identified nucleosome assembly protein 1 (NAP1)-like proteins NAP1L1 and NAP1L4 as novel DGKζ-interacting partners using a proteomic approach and revealed that these NAP1-like proteins induce cytoplasmic translocation of DGKζ in overexpressed cells because NAP1-like proteins associate with the nuclear localization signal of DGKζ and block its nuclear import via importin α...
November 2014: Histochemistry and Cell Biology
Hui Gong, Yuan Yan, Bo Fang, Yuanyuan Xue, Peipei Yin, Lu Li, Guoping Zhang, Xia Sun, Zhidan Chen, Hong Ma, Chunjie Yang, Yingjiong Ding, Ye Yong, Yichun Zhu, Huangtian Yang, Issei Komuro, Junbo Ge, Yunzeng Zou
Low efficiency of cardiomyocyte differentiation from induced pluripotent stem cells (iPSCs) hinders the clinical application of iPSC technology for cardiac repair strategy. Recently, we screened out nucleosome assembly protein 1-like 1 (Nap1l1), which was downregulated during the differentiation of P19CL6 cells into cardiomyocytes. Here, we attempted to study the role of Nap1l1 in cardiomyogenesis of iPSC. Nap1l1 was downregulated during the differentiation of iPSC. Knockdown of Nap1l1 dramatically enhanced the differentiation of iPSC into functional cardiomyocytes while overexpression of Nap1l1 sharply lowered the differentiation...
July 2014: Stem Cells
Lyudmila Y Kadyrova, Elena Rodriges Blanko, Farid A Kadyrov
Replication-coupled nucleosome assembly is a critical step in packaging newly synthesized DNA into chromatin. Previous studies have defined the importance of the histone chaperones CAF-1 and ASF1A, the replicative clamp PCNA, and the clamp loader RFC for the assembly of nucleosomes during DNA replication. Despite significant progress in the field, replication-coupled nucleosome assembly is not well understood. One of the complications in elucidating the mechanisms of replication-coupled nucleosome assembly is the lack of a defined system that faithfully recapitulates this important biological process in vitro...
October 15, 2013: Cell Cycle
Lucia Brandimarte, Valentina Pierini, Danika Di Giacomo, Chiara Borga, Filomena Nozza, Paolo Gorello, Marco Giordan, Giovanni Cazzaniga, Geertruy Te Kronnie, Roberta La Starza, Cristina Mecucci
The MLLT10 gene, located at 10p13, is a known partner of MLL and PICALM in specific leukemic fusions generated from recurrent 11q23 and 11q14 chromosome translocations. Deep sequencing recently identified NAP1L1/12q21 as another MLLT10 partner in T-cell acute lymphoblastic leukemia (T-ALL). In pediatric T-ALL, we have identified 2 RNA processing genes, that is, HNRNPH1/5q35 and DDX3X/Xp11.3 as new MLLT10 fusion partners. Gene expression profile signatures of the HNRNPH1- and DDX3X-MLLT10 fusions placed them in the HOXA subgroup...
June 20, 2013: Blood
Zhaoyu Li, Paul Gadue, Kaifu Chen, Yang Jiao, Geetu Tuteja, Jonathan Schug, Wei Li, Klaus H Kaestner
Nucleosome occupancy is fundamental for establishing chromatin architecture. However, little is known about the relationship between nucleosome dynamics and initial cell lineage specification. Here, we determine the mechanisms that control global nucleosome dynamics during embryonic stem (ES) cell differentiation into endoderm. Both nucleosome depletion and de novo occupation occur during the differentiation process, with higher overall nucleosome density after differentiation. The variant histone H2A.Z and the winged helix transcription factor Foxa2 both act to regulate nucleosome depletion and gene activation, thus promoting ES cell differentiation, whereas DNA methylation promotes nucleosome occupation and suppresses gene expression...
December 21, 2012: Cell
Kohji Nagano, Akunna Akpan, Gayathri Warnasuriya, Steven Corless, Nick Totty, Alice Yang, Robert Stein, Marketa Zvelebil, Allan Stensballe, Al Burlingame, Michael Waterfield, Rainer Cramer, John F Timms, Søren Naaby-Hansen
In Swiss 3T3 fibroblasts, long-term stimulation with PDGF, but not insulin-like growth factor 1 (IGF-1) or EGF, results in the establishment of an elongated migratory phenotype, characterized by the formation of retractile dendritic protrusions and absence of actin stress fibers and focal adhesion complexes. To identify receptor tyrosine kinase-specific reorganization of the Swiss 3T3 proteome during phenotypic differentiation, we compared changes in the pattern of protein synthesis and phosphorylation during long-term exposure to PDGF, IGF-1, EGF, and their combinations using 2DE-based proteomics after (35)S- and (33)P-metabolic labeling...
December 2012: Molecular & Cellular Proteomics: MCP
Lu Li, Hui Gong, Hongxiu Yu, Xiaohui Liu, Qingping Liu, Guoquan Yan, Yang Zhang, Haojie Lu, Yunzeng Zou, Pengyuan Yang
Transplantation of cardiomyocytes derived from stem cells is a promising option for cardiac repair. However, how to obtain efficient cardiomyocytes from stem cells is still a great challenge. Understanding of the mechanism that regulates the cardiac differentiation of stem cells is necessary for the effective induction of cardiomyocytes. A clonal derivative named P19CL6 cells can easily differentiate into cardiomyocytes with 1% dimethyl sulfoxide (DMSO) treatment, which offers a valuable model to study cardiomyocytes differentiation in vitro...
December 2012: Journal of Cellular Biochemistry
Qianru He, Lili Man, Yuhua Ji, Fei Ding
Schwann cells (SCs) express distinct sensory and motor phenotypes, which are associated with modality-specific promotion of axon growth. Here we compared cell proliferation and migration of primary cultured sensory and motor SCs and determined the mRNA expression of several genes, nap1l1, dok4, lpp, mmp-9 and l1cam, in two phenotypes of SCs. The results showed that the rate of cell proliferation or migration was higher in sensory SCs than in motor SCs, and the five proliferation or migration-related genes also had higher expression in sensory SCs than in motor SCs...
July 11, 2012: Neuroscience Letters
Francesca Guidi, Michele Puglia, Chiara Gabbiani, Ida Landini, Tania Gamberi, Dolores Fregona, Maria Agostina Cinellu, Stefania Nobili, Enrico Mini, Luca Bini, Pietro Amedeo Modesti, Alessandra Modesti, Luigi Messori
Cytotoxic gold compounds hold today great promise as new pharmacological agents for treatment of human ovarian carcinoma; yet, their mode of action is still largely unknown. To shed light on the underlying molecular mechanisms, we performed 2D-DIGE analysis to identify differential protein expression in a cisplatin-sensitive human ovarian cancer cell line (A2780/S) following treatment with two representative gold(iii) complexes that are known to be potent antiproliferative agents, namely AuL12 and Au(2)Phen...
April 2012: Molecular BioSystems
Masashi Okada, Yasukazu Hozumi, Tohru Ichimura, Toshiaki Tanaka, Hiroshi Hasegawa, Masakazu Yamamoto, Nobuya Takahashi, Ken Iseki, Hitoshi Yagisawa, Takashi Shinkawa, Toshiaki Isobe, Kaoru Goto
Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGKζ, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGKζ...
December 10, 2011: Experimental Cell Research
Mikaël Attia, Andreas Förster, Christophe Rachez, Paul Freemont, Philip Avner, Ute Christine Rogner
Mammals possess five nucleosome assembly protein 1-like (NAP1L) proteins, with three of them being expressed exclusively in the nervous system. The biological importance of the neuron-specific NAP1L2 protein is demonstrated by the neural tube defects occurring during the embryonic development of Nap1l2 mutant mice, which are associated with an overproliferation of neural stem cells and decreased neuronal differentiation. NAP1L2 controls the expression of its target genes, such as the cell cycle regulator Cdkn1c, at least in part via an effect on histone acetylation...
April 15, 2011: Journal of Molecular Biology
S Chamayou, G Bonaventura, C Alecci, D Tibullo, F Di Raimondo, A Guglielmino, M L Barcellona
INTRODUCTION: We studied the consequences of freezing/thawing processes on mRNA contents in MII oocytes after slow-freezing/rapid thawing (SF/RT) and vitrification/warming (V/W) protocols, and compared the results to fresh MII oocytes. We quantified the nuclear transcript mRNA responsible for the translation of proteins belonging either to trans-regulatory protein family or to functional structural proteins such as proteins involved in DNA structural organization (NAP1L1, TOP1, H1F0H1), chromosomal structure maintenance (SMC, SCC3, RAD21, SMC1A, SMC1B, STAG3, REC8), mitochondrial energetic pathways (ATP5GJ, SDHC), cell cycle regulation and processes (CLTA, MAPK6, CKS2) and staminal cell potency-development competence stage (DPPA3, OCT4, FOXJ2)...
April 2011: Cryobiology
Fredrick O Onono, Michael A Morgan, H Peter Spielmann, Douglas A Andres, Thangaiah Subramanian, Arnold Ganser, Christoph W M Reuter
Prenylation is a post-translational modification critical for the proper function of multiple physiologically important proteins, including small G-proteins, such as Ras. Methods allowing rapid and selective detection of protein farnesylation and geranylgeranylation are fundamental for the understanding of prenylated protein function and for monitoring efficacy of drugs such as farnesyltransferase inhibitors (FTIs). Although the natural substrates for prenyltransferases are farnesyl pyrophosphate and geranylgeranyl pyrophosphate, farnesyltransferase has been shown to incorporate isoprenoid analogues into protein substrates...
April 2010: Molecular & Cellular Proteomics: MCP
Ignat Drozdov, Mark Kidd, Boaz Nadler, Robert L Camp, Shrikant M Mane, Oyvind Hauso, Bjorn I Gustafsson, Irvin M Modlin
BACKGROUND: A more accurate taxonomy of small intestinal (SI) neuroendocrine tumors (NETs) is necessary to accurately predict tumor behavior and prognosis and to define therapeutic strategy. In this study, the authors identified a panel of such markers that have been implicated in tumorigenicity, metastasis, and hormone production and hypothesized that transcript levels of the genes melanoma antigen family D2 (MAGE-D2), metastasis-associated 1 (MTA1), nucleosome assembly protein 1-like (NAP1L1), Ki-67 (a marker of proliferation), survivin, frizzled homolog 7 (FZD7), the Kiss1 metastasis suppressor (Kiss1), neuropilin 2 (NRP2), and chromogranin A (CgA) could be used to define primary SI NETs and to predict the development of metastases...
April 15, 2009: Cancer
Kjell Oberg
PURPOSE OF REVIEW: Gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs) originate from cells of the diffuse endocrine system. Most GEP-NETs are sporadic, however, some of them, especially pancreatic endocrine tumors, may occur as part of familial syndromes. The genetic and molecular pathology of neuroendocrine tumor development is incomplete and remains largely unknown. However, the WHO classification introduced in clinical practice will give more insight into genetic and molecular changes related to tumor subtypes...
February 2009: Current Opinion in Endocrinology, Diabetes, and Obesity
Chi-Hwa Wu, Debashis Sahoo, Constadina Arvanitis, Nicole Bradon, David L Dill, Dean W Felsher
The MYC oncogene has been implicated in the regulation of up to thousands of genes involved in many cellular programs including proliferation, growth, differentiation, self-renewal, and apoptosis. MYC is thought to induce cancer through an exaggerated effect on these physiologic programs. Which of these genes are responsible for the ability of MYC to initiate and/or maintain tumorigenesis is not clear. Previously, we have shown that upon brief MYC inactivation, some tumors undergo sustained regression. Here we demonstrate that upon MYC inactivation there are global permanent changes in gene expression detected by microarray analysis...
June 2008: PLoS Genetics
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