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2004

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University of Massachusetts Medical School

Cell and Developmental Biology

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Articles 1 - 16 of 16

Full-Text Articles in Life Sciences

Regulation Of Cell Cycle By The Anaphase Spindle Midzone, Maki Murata-Hori, Greenfield Sluder, Yu-Li Wang Dec 2004

Regulation Of Cell Cycle By The Anaphase Spindle Midzone, Maki Murata-Hori, Greenfield Sluder, Yu-Li Wang

Open Access Articles

BACKGROUND: A number of proteins accumulate in the spindle midzone and midbody of dividing animal cells. Besides proteins essential for cytokinesis, there are also components essential for interphase functions, suggesting that the spindle midzone and/or midbody may play a role in regulating the following cell cycle.

RESULTS: We microsurgically severed NRK epithelial cells during anaphase or telophase, such that the spindle midzone/midbody was associated with only one of the daughter cells. Time-lapse recording of cells severed during early anaphase indicated that the cell with midzone underwent cytokinesis-like cortical contractions and progressed normally through the interphase, whereas the cell ...


Overexpression Of Glycine-Extended Gastrin Inhibits Parietal Cell Loss And Atrophy In The Mouse Stomach, Guanglin Cui, Theodore J. Koh, Duan Chen, Chun-Mei Zhao, Shigeo Takaishi, Graham J. Dockray, Andrea Varro, Arlin B. Rogers, James G. Fox, Timothy C. Wang Nov 2004

Overexpression Of Glycine-Extended Gastrin Inhibits Parietal Cell Loss And Atrophy In The Mouse Stomach, Guanglin Cui, Theodore J. Koh, Duan Chen, Chun-Mei Zhao, Shigeo Takaishi, Graham J. Dockray, Andrea Varro, Arlin B. Rogers, James G. Fox, Timothy C. Wang

Open Access Articles

Recently we have reported synergistic effects between glycine-extended gastrin (G-gly) and amidated gastrin-17 on acid secretion in short-term infusion studies. In the present study, we examined the long-term effect of G-gly on the atrophy-promoting effects of amidated gastrin in the mouse stomach with or without Helicobacter infection. Transgenic mice overexpressing amidated gastrin (INS-GAS mice), G-gly (MTI/G-gly mice), and both peptides (INS-GAS/G-gly mice) were used for assessment of acid secretion and ulcer susceptibility and histologic examination and scoring of preneoplastic lesions in response to the 3 and 6 months Helicobacter felis (H. felis) infection. We found that MTI/G-gly ...


Inducible Changes In Cell Size And Attachment Area Due To Expression Of A Mutant Swi/Snf Chromatin Remodeling Enzyme, David A. Hill, Simion I. Chiosea, Saha Jamaluddin, Kanaklata Roy, Andrew H. Fischer, Douglas D. Boyd, Jeffrey A. Nickerson, Anthony N. Imbalzano Nov 2004

Inducible Changes In Cell Size And Attachment Area Due To Expression Of A Mutant Swi/Snf Chromatin Remodeling Enzyme, David A. Hill, Simion I. Chiosea, Saha Jamaluddin, Kanaklata Roy, Andrew H. Fischer, Douglas D. Boyd, Jeffrey A. Nickerson, Anthony N. Imbalzano

Open Access Articles

The SWI/SNF enzymes belong to a family of ATP-dependent chromatin remodeling enzymes that have been functionally implicated in gene regulation, development, differentiation and oncogenesis. BRG1, the catalytic core subunit of some of the SWI/SNF enzymes, can interact with known tumor suppressor proteins and can act as a tumor suppressor itself. We report that cells that inducibly express ATPase-deficient versions of BRG1 increase in cell volume, area of attachment and nuclear size upon expression of the mutant BRG1 protein. Examination of focal adhesions reveals qualitative changes in paxillin distribution but no difference in the actin cytoskeletal structure. Increases in ...


Mitochondrial Remodeling In Adipose Tissue Associated With Obesity And Treatment With Rosiglitazone, Leanne Wilson-Fritch, Sarah M. Nicoloro, My T. Chouinard, Mitchell A. Lazar, Patricia C. Chui, John D. Leszyk, Juerg R. Straubhaar, Michael P. Czech, Silvia Corvera Nov 2004

Mitochondrial Remodeling In Adipose Tissue Associated With Obesity And Treatment With Rosiglitazone, Leanne Wilson-Fritch, Sarah M. Nicoloro, My T. Chouinard, Mitchell A. Lazar, Patricia C. Chui, John D. Leszyk, Juerg R. Straubhaar, Michael P. Czech, Silvia Corvera

Open Access Articles

Adipose tissue plays a central role in the control of energy homeostasis through the storage and turnover of triglycerides and through the secretion of factors that affect satiety and fuel utilization. Agents that enhance insulin sensitivity, such as rosiglitazone, appear to exert their therapeutic effect through adipose tissue, but the precise mechanisms of their actions are unclear. Rosiglitazone changes the morphological features and protein profiles of mitochondria in 3T3-L1 adipocytes. To examine the relevance of these effects in vivo, we studied white adipocytes from ob/ob mice during the development of obesity and after treatment with rosiglitazone. The levels of ...


The 4q Subtelomere Harboring The Fshd Locus Is Specifically Anchored With Peripheral Heterochromatin Unlike Most Human Telomeres, Rose Tam, Kelly P. Smith, Jeanne B. Lawrence Oct 2004

The 4q Subtelomere Harboring The Fshd Locus Is Specifically Anchored With Peripheral Heterochromatin Unlike Most Human Telomeres, Rose Tam, Kelly P. Smith, Jeanne B. Lawrence

Open Access Articles

This paper investigates the nuclear localization of human telomeres and, specifically, the 4q35 subtelomere mutated in facioscapulohumeral dystrophy (FSHD). FSHD is a common muscular dystrophy that has been linked to contraction of D4Z4 tandem repeats, widely postulated to affect distant gene expression. Most human telomeres, such as 17q and 17p, avoid the nuclear periphery to reside within the internal, euchromatic compartment. In contrast, 4q35 localizes at the peripheral heterochromatin with 4p more internal, generating a reproducible chromosome orientation that we relate to gene expression profiles. Studies of hybrid and translocation cell lines indicate this localization is inherent to the distal ...


Mitochondrial Survivin Inhibits Apoptosis And Promotes Tumorigenesis, Takehiko Dohi, Elena Beltrami, Nathan R. Wall, Janet Plescia, Dario C. Altieri Oct 2004

Mitochondrial Survivin Inhibits Apoptosis And Promotes Tumorigenesis, Takehiko Dohi, Elena Beltrami, Nathan R. Wall, Janet Plescia, Dario C. Altieri

Open Access Articles

Evasion of apoptosis is a hallmark of cancer, but the molecular circuitries of this process are not understood. Here we show that survivin, a member of the inhibitor of apoptosis gene family that is overexpressed in cancer, exists in a novel mitochondrial pool in tumor cells. In response to cell death stimulation, mitochondrial survivin is rapidly discharged in the cytosol, where it prevents caspase activation and inhibits apoptosis. Selective targeting of survivin to mitochondria enhances colony formation in soft agar, accelerates tumor growth in immunocompromised animals, and abolishes tumor cell apoptosis in vivo. Therefore, mitochondrial survivin orchestrates a novel pathway ...


Smooth Muscle Archvillin: A Novel Regulator Of Signaling And Contractility In Vascular Smooth Muscle, Samudra S. Gangopadhyay, Norio Takizawa, Cynthia Gallant, Amy L. Barber, Hyun-Dong Je, Tara C. Smith, Elizabeth J. Luna, Kathleen G. Morgan Sep 2004

Smooth Muscle Archvillin: A Novel Regulator Of Signaling And Contractility In Vascular Smooth Muscle, Samudra S. Gangopadhyay, Norio Takizawa, Cynthia Gallant, Amy L. Barber, Hyun-Dong Je, Tara C. Smith, Elizabeth J. Luna, Kathleen G. Morgan

Women’s Health Research Faculty Publications

The mechanisms by which protein kinase C (PKC) and extracellular-signal-regulated kinases (ERK1/2) govern smooth-muscle contractility remain unclear. Calponin (CaP), an actin-binding protein and PKC substrate, mediates signaling through ERK1/2. We report here that CaP sequences containing the CaP homology (CH) domain bind to the C-terminal 251 amino acids of smooth-muscle archvillin (SmAV), a new splice variant of supervillin, which is a known actin- and myosin-II-binding protein. The CaP-SmAV interaction is demonstrated by reciprocal yeast two-hybrid and blot-overlay assays and by colocalization in COS-7 cells. In differentiated smooth muscle, endogenous SmAV and CaP co-fractionate and co-translocate to the cell ...


Selective Modulation Of Type 1 Insulin-Like Growth Factor Receptor Signaling And Functions By Beta1 Integrins, Hira Lal Goel, Mara Fornaro, Loredana Moro, Natalia Teider, Johng S. Rhim, Michael King, Lucia R. Languino Aug 2004

Selective Modulation Of Type 1 Insulin-Like Growth Factor Receptor Signaling And Functions By Beta1 Integrins, Hira Lal Goel, Mara Fornaro, Loredana Moro, Natalia Teider, Johng S. Rhim, Michael King, Lucia R. Languino

Open Access Articles

We show here that beta1 integrins selectively modulate insulin-like growth factor type I receptor (IGF-IR) signaling in response to IGF stimulation. The beta1A integrin forms a complex with the IGF-IR and insulin receptor substrate-1 (IRS-1); this complex does not promote IGF-I mediated cell adhesion to laminin (LN), although it does support IGF-mediated cell proliferation. In contrast, beta1C, an integrin cytoplasmic variant, increases cell adhesion to LN in response to IGF-I and its down-regulation by a ribozyme prevents IGF-mediated adhesion to LN. Moreover, beta1C completely prevents IGF-mediated cell proliferation and tumor growth by inhibiting IGF-IR auto-phosphorylation in response to IGF-I stimulation ...


A Novel Phosphatidylinositol(3,4,5)P3 Pathway In Fission Yeast, Prasenjit Mitra, Yingjie Zhang, Lucia E. Rameh, Mariya P. Ivshina, Dannel Mccollum, John J. Nunnari, Gregory M. Hendricks, Monica L. Kerr, Seth J. Field, Lewis C. Cantley, Alonzo H. Ross Jul 2004

A Novel Phosphatidylinositol(3,4,5)P3 Pathway In Fission Yeast, Prasenjit Mitra, Yingjie Zhang, Lucia E. Rameh, Mariya P. Ivshina, Dannel Mccollum, John J. Nunnari, Gregory M. Hendricks, Monica L. Kerr, Seth J. Field, Lewis C. Cantley, Alonzo H. Ross

Open Access Articles

The mammalian tumor suppressor, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), inhibits cell growth and survival by dephosphorylating phosphatidylinositol-(3,4,5)-trisphosphate (PI[3,4,5]P3). We have found a homologue of PTEN in the fission yeast, Schizosaccharomyces pombe (ptn1). This was an unexpected finding because yeast (S. pombe and Saccharomyces cerevisiae) lack the class I phosphoinositide 3-kinases that generate PI(3,4,5)P3 in higher eukaryotes. Indeed, PI(3,4,5)P3 has not been detected in yeast. Surprisingly, upon deletion of ptn1 in S. pombe, PI(3,4,5)P3 became detectable at ...


Life, Death And E2f: Linking Proliferation Control And Dna Damage Signaling Via E2f1, Harry A. Rogoff, Timothy F. Kowalik Jun 2004

Life, Death And E2f: Linking Proliferation Control And Dna Damage Signaling Via E2f1, Harry A. Rogoff, Timothy F. Kowalik

Open Access Articles

Proper regulation of cellular proliferation is critical for normal development and cancer prevention. Most, if not all, cancer cells contain mutations in the Rb/E2F pathway, which controls cellular proliferation. Inactivation of the retinoblastoma (Rb) family of proteins can occur through Rb loss, mutation, or inactivation by cellular or viral oncoproteins leading to unrestrained proliferation and, often times, results in apoptosis. The loss of growth control occurs primarily by derepression and activation of the E2F transcription factors. E2F1 in particular, serves as the primary link between loss of Rb function and activation of p53-dependent apoptosis. E2F1 function is crucial for ...


Cell Cycle Progression After Cleavage Failure: Mammalian Somatic Cells Do Not Possess A "Tetraploidy Checkpoint", Yumi Uetake, Greenfield Sluder Jun 2004

Cell Cycle Progression After Cleavage Failure: Mammalian Somatic Cells Do Not Possess A "Tetraploidy Checkpoint", Yumi Uetake, Greenfield Sluder

Open Access Articles

Failure of cells to cleave at the end of mitosis is dangerous to the organism because it immediately produces tetraploidy and centrosome amplification, which is thought to produce genetic imbalances. Using normal human and rat cells, we reexamined the basis for the attractive and increasingly accepted proposal that normal mammalian cells have a "tetraploidy checkpoint" that arrests binucleate cells in G1, thereby preventing their propagation. Using 10 microM cytochalasin to block cleavage, we confirm that most binucleate cells arrest in G1. However, when we use lower concentrations of cytochalasin, we find that binucleate cells undergo DNA synthesis and later proceed ...


In Vitro Frap Reveals The Atp-Dependent Nuclear Mobilization Of The Exon Junction Complex Protein Srm160, Stefan Wagner, Simion I. Chiosea, Mariya P. Ivshina, Jeffrey A. Nickerson Mar 2004

In Vitro Frap Reveals The Atp-Dependent Nuclear Mobilization Of The Exon Junction Complex Protein Srm160, Stefan Wagner, Simion I. Chiosea, Mariya P. Ivshina, Jeffrey A. Nickerson

Open Access Articles

We present a new in vitro system for characterizing the binding and mobility of enhanced green fluorescent protein (EGFP)-labeled nuclear proteins by fluorescence recovery after photobleaching in digitonin-permeabilized cells. This assay reveals that SRm160, a splicing coactivator and component of the exon junction complex (EJC) involved in RNA export, has an adenosine triphosphate (ATP)-dependent mobility. Endogenous SRm160, lacking the EGFP moiety, could also be released from sites at splicing speckled domains by an ATP-dependent mechanism. A second EJC protein, RNPS1, also has an ATP-dependent mobility, but SRm300, a protein that binds to SRm160 and participates with it in ...


Disruption Of Gradient Expression Of Zic3 Resulted In Abnormal Intra-Retinal Axon Projection, Jinhua Zhang, Zhe Jin, Zheng-Zheng Bao Feb 2004

Disruption Of Gradient Expression Of Zic3 Resulted In Abnormal Intra-Retinal Axon Projection, Jinhua Zhang, Zhe Jin, Zheng-Zheng Bao

Open Access Articles

The targeting of retinal ganglion axons toward the optic disc is the first step in axon pathfinding in the visual system. The molecular mechanisms involved in guiding the retinal axons to project towards the optic disc are not well understood. We report that a gene encoding a zinc-finger transcription factor, Zic3, is expressed in a periphery-high and center-low gradient in the retina at the stages of active axon extension inside the retina. The gradient expression of Zic3 recedes towards the periphery over the course of development, correlating with the progression of retinal cell differentiation and axonogenesis. Disruption of gradient expression ...


Expression Of Rag2 And V(D)J Recombinase Activity Are Reduced In Aged Mice As A Result Of Changes In The Bone Marrow Microenvironment: A Dissertation, Joseph E. Labrie Iii Feb 2004

Expression Of Rag2 And V(D)J Recombinase Activity Are Reduced In Aged Mice As A Result Of Changes In The Bone Marrow Microenvironment: A Dissertation, Joseph E. Labrie Iii

GSBS Dissertations and Theses

Both humans and mice display an age-related decline in immunity. Reduced generation of mature B cells may be a contributing factor due to reduced entry of mature B cells with novel B cell receptors and specificity for pathogens into the mature B cell pool. In aged mice the numbers of B cell precursors within the bone marrow are diminished; there is a severe reduction in numbers of pre-B cells and an increase in numbers of re-circulated mature B cells. Other defects in developing B cells include reduced expression of rag1 and rag2 when measured in total bone marrow precursor populations ...


Cyclin-Dependent Kinase 5 Phosphorylates The N-Terminal Domain Of The Postsynaptic Density Protein Psd-95 In Neurons, Maria A. Morabito, Morgan Sheng, Li-Huei Tsai Jan 2004

Cyclin-Dependent Kinase 5 Phosphorylates The N-Terminal Domain Of The Postsynaptic Density Protein Psd-95 In Neurons, Maria A. Morabito, Morgan Sheng, Li-Huei Tsai

Morabito Lab Publications

PSD-95 (postsynaptic density 95) is a postsynaptic scaffolding protein that links NMDA receptors to the cytoskeleton and signaling molecules. The N-terminal domain of PSD-95 is involved in the synaptic targeting and clustering of PSD-95 and in the clustering of NMDA receptors at synapses. The N-terminal domain of PSD-95 contains three consensus phosphorylation sites for cyclin-dependent kinase 5 (cdk5), a proline-directed serine-threonine kinase essential for brain development and implicated in synaptic plasticity, dopamine signaling, cocaine addiction, and neurodegenerative disorders. We report that PSD-95 is phosphorylated in the N-terminal domain by cdk5 in vitro and in vivo, and that this phosphorylation is ...


Glycine-Extended Gastrin Promotes The Growth Of Lung Cancer, Theodore J. Koh, John K. Field, Andrea Varro, Triantafillos Liloglou, Pat Fielding, Guanglin Cui, Jeanmarie Houghton, Graham J. Dockray, Timothy C. Wang Jan 2004

Glycine-Extended Gastrin Promotes The Growth Of Lung Cancer, Theodore J. Koh, John K. Field, Andrea Varro, Triantafillos Liloglou, Pat Fielding, Guanglin Cui, Jeanmarie Houghton, Graham J. Dockray, Timothy C. Wang

Open Access Articles

The less processed forms of gastrin have recently been shown to act as trophic factors for both normal and malignant colonic cells. Although incompletely processed forms of gastrin such as glycine-extended gastrin and progastrin are also expressed in human lung cancers, the clinical significance of this expression has not been addressed. Consequently, we investigated the effects of overexpression of glycine-extended gastrin in a mouse strain that is prone to developing lung cancer and also examined the expression of incompletely processed gastrins in primary human lung cancers. We found that transgenic overexpression of glycine-extended gastrin in FVB/N mice resulted in ...