The nuclear envelope proteins, Nesprins, have been primarily studied during interphase where they function in maintaining nuclear shape, size, and positioning. We analyze here the function of Nesprin-2 in chromatin interactions in interphase and dividing cells. We characterize a region in the rod domain of Nesprin-2 that is predicted as SMC domain (aa 1436&#x2013;1766). We show that this domain can interact with itself. It furthermore has the capacity to bind to SMC2 and SMC4, the core subunits of condensin. The interaction was observed during all phases of the cell cycle; it was particularly strong during S phase and persisted also during mitosis. Nesprin-2 knockdown did not affect condensin distribution; however we noticed significantly higher numbers of chromatin bridges in Nesprin-2 knockdown cells in anaphase. Thus, Nesprin-2 may have an impact on chromosomes which might be due to its interaction with condensins or to indirect mechanisms provided by its interactions at the nuclear envelope.

Xin Xing

Carmen Mro&#xdf;

Linlin Hao

Martina Munck

Alexandra Herzog

Clara Mohr

C. P. Unnikannan

Pranav Kelkar

Angelika A. Noegel

Ludwig Eichinger

Sascha Neumann

Nesprin-2 Interacts with Condensin Component SMC2

The serine protease thrombin activates Protease-Activated Receptors (PARs), a family of G-protein-coupled receptors (GPCRs) activated by the proteolytic cleavage of their extracellular N-terminal domain. Four members of this family have been identified: PAR1–4. The activation of Protease-Activated Receptor 1(PAR1), the prototype of this receptor family, leads to an increase in intracellular Ca+2 concentration ([Ca+2]i) mediated by <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-5.3006pt" id="M1" height="14.067pt" version="1.1" viewBox="-0.0498162 -8.7664 23.6013 14.067" width="23.6013pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g121-69" d="M692 302H438V274C537 267 543 260 543 188V103C543 61 531 48 511 37C489 26 458 20 424 20C231 20 146 188 146 333C146 517 258 630 411 630C507 630 582 597 606 474L634 480C627 546 622 601 619 636C586 643 510 665 426 665C230 665 44 552 44 321C44 122 191 -15 411 -15C491 -15 573 7 635 21C629 49 628 81 628 116V202C628 261 632 266 692 274V302Z"/></g><g transform="matrix(.0091,0,0,-0.0091,9.295,3.132)"><path id="g58-111" d="M523 -235V-204C453 -196 446 -194 446 -125V333C446 400 449 420 449 440L444 443C429 436 416 433 409 433C400 432 396 433 381 438C370 442 349 447 312 451C170 451 40 343 40 198C40 101 109 -12 258 -12L365 30V-124C365 -193 357 -196 277 -204V-235H523ZM365 63C344 54 320 47 289 47C217 47 132 110 132 231C132 348 201 407 267 407C300 407 342 392 365 365V63Z"/></g><g transform="matrix(.0091,0,0,-0.0091,14.054,3.132)"><path id="g50-50" d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z"/></g><g transform="matrix(.0091,0,0,-0.0091,18.486,3.132)"><use xlink:href="#g50-50"/></g></svg>α coupling and phospholipase C (PLC) activation. We have previously shown that the stimulation of PAR1 by thrombin promotes intracellular signaling leading to RPE cell transformation, proliferation, and migration which characterize fibroproliferative eye diseases leading to blindness. Within this context, the elucidation of the mechanisms involved in PAR1 inactivation is of utmost importance. Due to the irreversible nature of PAR1 activation, its inactivation must be efficiently regulated in order to terminate signaling. Using ARPE-19 human RPE cell line, we characterized thrombin-induced [Ca+2]i increase and demonstrated the calcium-dependent activation of μ-calpain mediated by PAR1. Calpains are a family of calcium-activated cysteine proteases involved in multiple cellular processes including the internalization of membrane proteins through clathrin-coated vesicles. We demonstrated that PAR1-induced calpain activation results in the degradation of α-spectrin by calpain, essential for receptor endocytosis, and the consequent decrease in PAR1 membrane expression. Collectively, the present results identify a novel μ-calpain-dependent mechanism for PAR1 inactivation following exposure to thrombin.

Alejandro Alvarez-Arce

Irene Lee-Rivera

Edith L&#xf3;pez

Arturo Hern&#xe1;ndez-Cruz

Ana Mar&#xed;a L&#xf3;pez-Colom&#xe9;

Thrombin-Induced Calpain Activation Promotes Protease-Activated Receptor 1 Internalization

It has been reported that water at the interface of a hydrophilic thin film forms an exclusion zone, which has a higher density than ordinary water. A similar phenomenon was observed for a hydrated hydrophilic ceramic powder, and water turns into a three-dimensional cell-like structure composed of high density water and low density water. This structured water appears to have a stimulative effect on plant growth. This report outlines our study of antioxidant properties of this structured water and its effect on cell bioactivities. Culturing media which were prepared utilizing this antioxidant structured water promoted the viability of RAW 264.7 macrophage cells by up to three times. The same tendency was observed for other cells including IEC-6, C2C12, and 3T3-L1. Also, the cytokine expression of the splenocytes taken from a mouse spleen increased in the same manner. The water also appears to suppress the viability of cancer cell, MCF-7. These results strongly suggest that the structured water helps the activities of normal cells while suppressing those of malignant cells.

Seong Gu Hwang

Ho-Sung Lee

Byung-Cheon Lee

GunWoong Bahng

Effect of Antioxidant Water on the Bioactivities of Cells

Tissue regeneration and repair have received much attention in the medical field over the years. The study of amphibians, such as newts and salamanders, has uncovered many of the processes that occur in these animals during full-limb/digit regeneration, a process that is highly limited in mammals. Understanding these processes in amphibians could shed light on how to develop and improve this process in mammals. Amputation injuries in mammals usually result in the formation of scar tissue with limited regrowth of the limb/digit; however, it has been observed that the very tips of digits (fingers and toes) can partially regrow in humans and mice under certain conditions. This review will summarize and compare the processes involved in salamander limb regeneration, mammalian wound healing, and digit regeneration in mice and humans.

Yohan Choi

Fanwei Meng

Charles S. Cox

Kevin P. Lally

Johnny Huard

Yong Li

Regeneration and Regrowth Potentials of Digit Tips in Amphibians and Mammals

The thrombopoietin (TPO) gene expression in human ovary and cancer cells from patients with ovarian carcinomatosis, as well as several cancer cell lines including MDA-MB231 (breast cancer), K562 and HL60 (Leukemic cells), OVCAR-3NIH and SKOV-3 (ovarian cancer), was performed using RT PCR, real-time PCR, and gene sequencing. Human liver tissues are used as controls. The presence of TPO in the cells and its regulation by activated protein C were explored by flow cytometry. TPO content of cell extract as well as plasma of a patient with ovarian cancer was evaluated by ELISA. The functionality of TPO was performed in coculture on the basis of the viability of a TPO-dependent cell line (Ba/F3), MTT assay, and Annexin-V labeling. As in liver, ovarian tissues and all cancer cells lines except the MDA-MB231 express the three TPO-1 (full length TPO), TPO-2 (12&#x2009;bp deletion), and TPO-3 (116&#x2009;pb deletion) variants. Primary ovarian cancer cells as well as cancer cell lines produce TPO. The thrombopoietin production by OVCAR-3 increased when cells are stimulated by aPC. OVCAR-3 cell&#x2019;s supernatant can replace exogenous TPO and inhibited TPO-dependent cell line (Ba/F3) apoptosis. The thrombopoietin produced by tumor may have a direct effect on thrombocytosis/thrombosis occurrence in patients with ovarian cancer.

Samaher Besbes

Shahid Shah

Iman Al-dybiat

Shahsoltan Mirshahi

Helene Helfer

Haythem Najah

Caroline Fourgeaud

Marc Pocard

Ibtissem Ghedira

Jeannette Soria

Massoud Mirshahi

Thrombopoietin Secretion by Human Ovarian Cancer Cells

Exposure to maternal cortisol plays a crucial role in fetal organogenesis. However, fetal overexposure to cortisol has been linked to a range of short- and long-term adverse outcomes. Normally, this is prevented by the expression of an enzyme in the placenta called 11-beta hydroxysteroid dehydrogenase type 2 (11&#x3b2;-HSD2) which converts active cortisol to its inactive metabolite cortisone. Placental 11&#x3b2;-HSD2 is known to be reduced in a number of adverse pregnancy complications, possibly through an epigenetic mechanism. As a result, a number of pan-HDAC inhibitors have been examined for their ability to promote 11&#x3b2;-HSD2 expression. However, it is not known if the effects of pan-HDAC inhibition are a general phenomenon or if the effects are dependent upon a specific class of HDACs. Here, we examined the ability of pan- and class-specific HDAC inhibitors to regulate 11&#x3b2;-HSD2 expression in JEG3 cells. We find that pan-, class I, or class IIa HDAC inhibition promoted 11&#x3b2;-HSD2 expression and prevented cortisol or interleukin-1&#x3b2;-induced decrease in its expression. These results demonstrate that targeting a specific class of HDACs can promote 11&#x3b2;-HSD2 expression in JEG3 cells. This adds to the growing body of evidence suggesting that HDACs may be crucial in maintaining normal fetal development.

Katie L. Togher

Louise C. Kenny

Gerard W. O&#x2019;Keeffe

Class-Specific Histone Deacetylase Inhibitors Promote 11-Beta Hydroxysteroid Dehydrogenase Type 2 Expression in JEG-3 Cells

The Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the &#x201c;master regulator&#x201d; of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate its role. Previously we identified various ubiquitination events on CIITA. Monoubiquitination is important for CIITA transactivity, while K63 linked ubiquitination is involved in crosstalk with ERK1/2 phosphorylation, where together they mediate cellular movement from the cytoplasm to nuclear region. Further, CIITA is also modified by degradative K48 polyubiquitination. However, the E3 ligase responsible for these modifications was unknown. We show CIITA ubiquitination and transactivity are enhanced with the histone acetyltransferase (HAT), p300/CBP associated factor (pCAF), and the E3 ligase region within pCAF is necessary for both. Additionally, pCAF mediated ubiquitination is independent of pCAF&#x2019;s HAT domain, and acetylation deficient CIITA is K48 polyubiquitinated and degraded in the presence of pCAF. Lastly, we identify the histone acetyltransferase, pCAF, as the E3 ligase responsible for CIITA&#x2019;s ubiquitination.

Julie E. Morgan

Susanna F. Greer

Pulling a Ligase out of a &#x201c;HAT&#x201d;: pCAF Mediates Ubiquitination of the Class II Transactivator

About this journal

International Journal of Cell Biology publishes original research articles as well as review articles in all areas of cell biology.

Journal profile

Meet the editorial board

International Journal of Cell Biology maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.

Editor spotlight

Submit your proposal

Do you think there is an emerging area of research that really needs to be highlighted? Or an existing research area that has been overlooked or would benefit from deeper investigation? Raise the profile of a research area by leading a Special Issue.

Special Issues

Author guidelines

Editorial board

Databases and indexing

International Journal of Cell Biology - Table of contents 2017

International Journal of Cell Biology | Hindawi

title

International Journal of Cell Biology publishes original research articles as well as review articles in all areas of cell biology.

International Journal of Cell Biology