The role of primer recognition proteins in DNA replication: association with nuclear matrix in Hela cells

Vishwanatha, Jamboor K.; Jindal, Hitesh K.; Davis, Randall G.

doi:10.1242/jcs.101.1.25

Cited by 96 publications

(9 citation statements)

References 29 publications

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“…Additionally, IPF lungs revealed pronounced up-regulation of the glycolytic enzyme PGK1. PGK1 not only functions in glycolysis, but also as a nuclear protein in DNA replication, and has been therefore related to cell proliferation. − In IPF, nuclear PGK1 expression was observed in bronchiolar basal cells of hyperplastic bronchioles, as well as in p-Hsp27 positive basal cells near active sites of fibrosis. Thus, up-regulation and nuclear translocation of PGK1 highlighted also bronchiolar basal cell proliferation and the process of bronchiolization in IPF.…”

Section: Discussionmentioning

confidence: 99%

Comparative Proteomic Analysis of Lung Tissue from Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lung Transplant Donor Lungs

Korfei

Schmitt²,

Ruppert

et al. 2011

J. Proteome Res.

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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease for which no effective therapy exists to date. To identify the molecular mechanisms underlying IPF, we performed comparative proteome analysis of lung tissue from patients with sporadic IPF (n = 14) and human donor lungs (controls, n = 10) using two-dimensional gel electrophoresis and MALDI-TOF-MS. Eighty-nine differentially expressed proteins were identified, from which 51 were up-regulated and 38 down-regulated in IPF. Increased expression of markers for the unfolded protein response (UPR), heat-shock proteins, and DNA damage stress markers indicated a chronic cell stress-response in IPF lungs. By means of immunohistochemistry, induction of UPR markers was encountered in type-II alveolar epithelial cells of IPF but not of control lungs. In contrast, up-regulation of heat-shock protein 27 (Hsp27) was exclusively observed in proliferating bronchiolar basal cells and associated with aberrant re-epithelialization at the bronchiolo-alveolar junctions. Among the down-regulated proteins in IPF were antioxidants, members of the annexin family, and structural epithelial proteins. In summary, our results indicate that IPF is characterized by epithelial cell injury, apoptosis, and aberrant epithelial proliferation.

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Section: Discussionmentioning

confidence: 99%

Comparative Proteomic Analysis of Lung Tissue from Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lung Transplant Donor Lungs

Korfei

Schmitt²,

Ruppert

et al. 2011

J. Proteome Res.

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“…PGK 1 catalyzes the reversible transfer of a phospho group from 1,3-bisphosphoglycerate (1, to ADP, yielding 3-phosphoglycerate (3-PG) and ATP during glycolysis. In addition, PGK was reported to influence DNA replication and repair in mammalian cell nuclei (1,2) and to stimulate viral mRNA synthesis in cytosol (3), and it may supply ATP for the Na 2+ and Ca 2+ ion pump (4,5). PGK also catalyzes phosphorylation of L-nucleoside analogues which are promising candidates for the inhibition of viral replication and treatment of cancer (6)(7)(8).…”

mentioning

confidence: 99%

“…PGK catalyzes the reversible transfer of a phospho group from 1,3-bisphosphoglycerate (1,3-BPG) to ADP, yielding 3-phosphoglycerate (3-PG) and ATP during glycolysis. In addition, PGK was reported to influence DNA replication and repair in mammalian cell nuclei ( , ) and to stimulate viral mRNA synthesis in cytosol (), and it may supply ATP for the Na 2+ and Ca 2+ ion pump ( , ). PGK also catalyzes phosphorylation of l -nucleoside analogues which are promising candidates for the inhibition of viral replication and treatment of cancer ( − ).…”

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confidence: 99%

Substrate-Assisted Movement of the Catalytic Lys 215 during Domain Closure: Site-Directed Mutagenesis Studies of Human 3-Phosphoglycerate Kinase

et al. 2005

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3-Phosphoglycerate kinase (PGK) is a two-domain hinge-bending enzyme. It is still unclear how the geometry of the active site is formed during domain closure and how the catalytic residues are brought into the optimal position for the reaction. Comparison of the three-dimensional structures in various open and closed conformations suggests a large (10 A) movement of Lys 215 during domain closure. This change would be required for direct participation of this side chain in both the catalyzed phospho transfer and the special anion-caused activation. To test the multiple roles of Lys 215, two mutants (K215A and K215R) were constructed from human PGK and characterized in enzyme kinetic and substrate binding studies. For comparison, mutants (R38A and R38K) of the known essential residue, Arg 38, were also produced. Drastic decreases (1500- and 500-fold, respectively), as in the case of R38A, were observed in the kcat values of mutants K215A and K215R, approving the essential catalytic role of Lys 215. In contrast, the R38K mutation caused an only 1.5-fold decrease in activity. This emphasizes the importance of a very precise positioning of Lys 215 in the active site, in addition to its positive charge. The side chain of Lys 215 is also responsible for the substrate and anion-dependent activation, since these properties are abolished upon mutation. Among the kinetic constants mainly the Km values of MgATP and 1,3-BPG are increased (approximately 20- and approximately 8-fold, respectively) in the case of the neutral K215A mutant, evidence of the interaction of Lys 215 with the transferring phospho group in the functioning complex. Weakening of MgATP binding (a moderate increase in Kd), but not of MgADP binding, upon mutation indicates an initial weak interaction of Lys 215 with the gamma-phosphate already in the nonfunctioning open conformation. Thus, during domain closure, Lys 215 possibly moves together with the transferring phosphate; meanwhile, this group is being positioned properly for catalysis.

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“…17 Furthermore, annexin A2 interacts with actin and plays a role in actin filament dynamics. 18 This annexin has also been detected in the nucleus, and in vitro experiments show that it can enhance DNA polymerase R. 19 In relation to tumorigenesis, several publications associate annexin A2 with cell proliferation, [20][21][22] migration and differentiation, 23,24 invasion, 25 angiogenesis, and metastasis. 26 However, the role of annexin A2 in cancer is controversial since it is upregulated in hepatocellular carcinoma, pancreatic adenocarcinoma, high-grade glioma, gastric carcinoma, acute promyelocytic leukemia, primary colorectal cancer, lung cancer, breast cancer, and cervical squamus cell carcinoma but downregulated in laryngeal or esophageal squamous cell carcinoma and prostate adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, annexin A2 interacts with actin and plays a role in actin filament dynamics . This annexin has also been detected in the nucleus, and in vitro experiments show that it can enhance DNA polymerase α . In relation to tumorigenesis, several publications associate annexin A2 with cell proliferation, − migration and differentiation, , invasion, angiogenesis, and metastasis .…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Annexin A2 Phosphorylation Induced by Microtubule Interfering Agents and Kinesin Spindle Protein Inhibitors

et al. 2010

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Microtubule interfering agents (MIAs) are antitumor drugs that inhibit microtubule dynamics, while kinesin spindle protein (KSP) inhibitors are substances that block the formation of the bipolar spindle during mitosis. All these compounds cause the accumulation of mitotic cells and subsequently cell death. We used two-dimensional gel electrophoresis (2DE) followed by MALDI-MS analysis to demonstrate that the MIAs vinblastine (Velban) and paclitaxel (Taxol), as well as the KSP inhibitor S-tritil-L-cysteine, induce the phosphorylation of annexin A2 in human lung carcinoma A549 cells. Further tandem mass spectrometry analysis using a combination of peptide fragmentation methods (CID and ETD) and multiple reaction monitoring (MRM) analysis determined that this modification occurs mainly at threonine 19. We show that MIAs and KSP inhibitors only induce this phosphorylation in cells capable of reaching the M phase. Furthermore, we demonstrate that CDK activity is required for the phosphorylation of annexin A2 induced by MIAs and KSP inhibitors. Finally, we have used double thymidine block synchronization to demonstrate that annexin A2 is not phosphorylated during a normal mitosis, indicating that this phosphorylation of annexin A2 is a specific response to these drugs.

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The role of primer recognition proteins in DNA replication: association with nuclear matrix in Hela cells

Cited by 96 publications

References 29 publications

Comparative Proteomic Analysis of Lung Tissue from Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lung Transplant Donor Lungs

Comparative Proteomic Analysis of Lung Tissue from Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lung Transplant Donor Lungs

Substrate-Assisted Movement of the Catalytic Lys 215 during Domain Closure: Site-Directed Mutagenesis Studies of Human 3-Phosphoglycerate Kinase

Proteomic Analysis of Annexin A2 Phosphorylation Induced by Microtubule Interfering Agents and Kinesin Spindle Protein Inhibitors

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