scholarly journals Transformation by Bovine Papillomavirus Type 1 E6 Requires Paxillin

2008 ◽  
Vol 82 (12) ◽  
pp. 5962-5966 ◽  
Author(s):  
Ramon Wade ◽  
Nicole Brimer ◽  
Scott Vande Pol
Keyword(s):  
Focal Adhesion ◽  
Essential Role ◽  
Consensus Sequence ◽  
Cellular Protein ◽  
Regulatory Proteins ◽  
Phosphorylation Sites ◽  
Bovine Papillomavirus ◽  
Independent Transformation

ABSTRACT Papillomavirus E6 proteins are adapters that change the function of cellular regulatory proteins. The bovine papillomavirus type 1 E6 (BE6) binds to LXXLL peptide sequences termed LD motifs (consensus sequence LDXLLXXL) on the cellular protein paxillin that is a substrate of Src and focal adhesion kinases. Anchorage-independent transformation induced by BE6 required both paxillin and BE6-binding LD motifs on paxillin but was independent of the major tyrosine phosphorylation sites of paxillin. The essential role of paxillin in transformation by BE6 highlights the role of paxillin in the transduction of cellular signals that result in anchorage-independent cell proliferation.

Abstract 110: Thrombospondin Type-1 Domain-Containing Protein 1 (THSD1), an Intracranial Aneurysm Susceptibility Gene, Mediates Cell Adhesion in Human Umbilical Vein Endothelial Cells

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Xiaoqian Fang ◽  
Dong H Kim ◽  
Teresa Santiago-Sim
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Focal Adhesion ◽  
Umbilical Vein ◽  
Adhesion Formation ◽  
Wild Type ◽  
Focal Adhesion Formation ◽  
Umbilical Vein Endothelial Cells

Introduction: An intracranial aneurysm (IA) is a weak spot in cerebral blood vessel wall that can lead to its abnormal bulging. Previously, we reported that mutations in THSD1 , encoding thrombospondin type-1 domain-containing protein 1, are associated with IA in a subset of patients. THSD1 is a transmembrane molecule with a thrombospondin type-1 repeat (TSR). Proteins with TSR domain have been implicated in a variety of processes including regulation of matrix organization, cell adhesion and migration. We have shown that in mouse brain Thsd1 is expressed in endothelial cells. Hypothesis: THSD1 plays an important role in maintaining the integrity of the endothelium by promoting adhesion of endothelial cells to the underlying basement membrane. Methods: Human umbilical vein endothelial cells are used to investigate the role of THSD1 in vitro . THSD1 expression was knocked-down by RNA interference. Cell adhesion assay was done on collagen I-coated plates and focal adhesion formation was visualized using immunofluorescence by paxillin and phosphorylated focal adhesion kinase (pFAK) staining. THSD1 re-expression is accomplished by transfection with a pCR3.1-THSD1-encoding plasmid. Results: Knockdown of THSD1 caused striking change in cell morphology and size. Compared to control siRNA-treated cells that exhibited typical cobblestone morphology, THSD1 knockdown cells were narrow and elongated, and were significantly smaller ( p <0.01). Cell adherence to collagen I-coated plates was also attenuated in THSD1 knockdown cells ( p <0.01). Consistent with this finding is the observation that the number and size of focal adhesions, based on paxillin and pFAK staining, were significantly reduced after THSD1 knockdown ( p <0.01). These defects in cell adhesion and focal adhesion formation were rescued by re-expression of wild type THSD1 ( p <0.05). In contrast, initial studies indicate that expression of mutated versions of THSD1 as seen in human patients (L5F, R450*, E466G, P639L) could not restore cell adhesion and focal adhesion formation to wild type levels. Conclusions: Our studies provide evidence for a role of THSD1 and THSD1 mutations in endothelial cell adhesion and suggest a possible mechanism underlying THSD1 -mediated aneurysm disease.

scholarly journals Essential role of submandibular lymph node dendritic cells in protective sublingual immunotherapy against murine allergy

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Noriaki Miyanaga ◽  
Hideaki Takagi ◽  
Tomofumi Uto ◽  
Tomohiro Fukaya ◽  
Junta Nasu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Essential Role ◽  
Sublingual Immunotherapy ◽  
Specific Treatment ◽  
Mucosal Tolerance ◽  
Submandibular Lymph Node ◽  
Dendritic Cell Subsets ◽  
Allergic Disorders

AbstractWhile sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear. Here, we show the prerequisite role of conventional dendritic cells in submandibular lymph nodes (ManLNs) in the effectiveness of SLIT for the treatment of allergic disorders in mice. Deficiency of conventional dendritic cells or CD4+Foxp3+ regulatory T (Treg) cells abrogates the protective effect of SLIT against allergic disorders. Furthermore, sublingual antigenic application primarily induces antigen-specific CD4+Foxp3+ Treg cells in draining ManLNs, in which it is severely impaired in the absence of cDCs. In ManLNs, migratory CD11b+ cDCs are superior to other conventional dendritic cell subsets for the generation of antigen-specific CD4+Foxp3+ Treg cells, which is reflected by their dominancy in the tolerogenic features to favor this program. Thus, ManLNs are privileged sites in triggering mucosal tolerance mediating protect effect of SLIT on allergic disorders that requires a tolerogenesis of migratory CD11b+ conventional dendritic cells.

scholarly journals The Mechanism of Budding of Retroviruses from Cell Membranes

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew Pincetic ◽  
Jonathan Leis
Keyword(s):  
Protein Complexes ◽  
Cellular Protein ◽  
Multivesicular Bodies ◽  
Escrt Machinery ◽  
Immunodeficiency Virus ◽  
Cellular Machinery ◽  
Avian Sarcoma ◽  
Hiv 1

Retroviruses have evolved a mechanism for the release of particles from the cell membrane that appropriates cellular protein complexes, referred to as ESCRT-I, -II, -III, normally involved in the biogenesis of multivesicular bodies. Three different classes of late assembly (L) domains encoded in Gag, with core sequences of PPXY, PTAP, and YPXL, recruit different components of the ESCRT machinery to form a budding complex for virus release. Here, we highlight recent progress in identifying the role of different ESCRT complexes in facilitating budding, ubiquitination, and membrane targeting of avian sarcoma and leukosis virus (ASLV) and human immunodeficiency virus, type 1 (HIV-1). These findings show that retroviruses may adopt parallel budding pathways by recruiting different host factors from common cellular machinery for particle release.

scholarly journals p38 mitogen-activated protein kinase is crucial for bovine papillomavirus type-1 transformation of equine fibroblasts

2011 ◽  
Vol 92 (8) ◽  
pp. 1778-1786 ◽  
Author(s):  
ZhengQiang Yuan ◽  
Elizabeth A. Gault ◽  
M. Saveria Campo ◽  
Lubna Nasir
Keyword(s):  
Protein Kinase ◽  
Viral Gene Expression ◽  
Cellular Transformation ◽  
Mitogen Activated Protein Kinase ◽  
Viral Gene ◽  
Bovine Papillomavirus ◽  
Equine Sarcoid ◽  
Mitogen Activated Protein

Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type-1 (BPV-1) and less commonly BPV-2 are the causative agents of the diseases. It has been demonstrated that BPV-1 viral gene expression is necessary for maintaining the transformation phenotype. However, the underlying mechanism for BPV-1 transformation remains largely unknown, and the cellular factors involved in transformation are not fully understood. Previously mitogen-activated protein kinase (MAPK) signalling pathway has been shown to be important for cellular transformation. This study investigated the role of p38 MAPK (p38) in the transformation of equine fibroblasts by BPV-1. Elevated expression of phosphorylated p38 was observed in BPV-1 expressing fibroblasts due to the expression of BPV-1 E5 and E6. The phosphorylation of the MK2 kinase, a substrate of p38, was also enhanced. Inhibition of p38 activity by its selective inhibitor SB203580 changed cell morphology, reduced the proliferation of sarcoid fibroblasts and inhibited cellular invasiveness, indicating the indispensable role of p38 in BPV-1 transformation of equine fibroblasts. These findings provide new insights into the pathogenesis of equine sarcoids and suggest that p38 could be a potential target for equine sarcoid therapy.

scholarly journals Focal Adhesion Kinases in Adhesion Structures and Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Pierre P. Eleniste ◽  
Angela Bruzzaniti
Keyword(s):  
Focal Adhesion ◽  
Structural Design ◽  
Tyrosine Kinases ◽  
Essential Role ◽  
Focal Adhesions ◽  
Basic Function ◽  
Contact Structures ◽  
Wide Range ◽  
Compare And Contrast

Cell adhesion to the extracellular matrix (ECM) is essential for cell migration, proliferation, and embryonic development. Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. In this paper, we compare and contrast the basic organization and role of focal adhesions, podosomes, and invadopodia in different cells. In addition, we discuss the role of the tyrosine kinases, FAK, Pyk2, and Src, which are critical for the function of the different adhesion structures. Finally, we discuss the essential role of these tyrosine kinases from the perspective of human diseases.

scholarly journals The Mason-Pfizer Monkey Virus PPPY and PSAP Motifs Both Contribute to Virus Release

2003 ◽  
Vol 77 (17) ◽  
pp. 9474-9485 ◽  
Author(s):  
Eva Gottwein ◽  
Jochen Bodem ◽  
Barbara Müller ◽  
Ariane Schmechel ◽  
Hanswalter Zentgraf ◽  
...  
Keyword(s):  
Cellular Protein ◽  
Membrane Curvature ◽  
Mutant Virus ◽  
Dependent Manner ◽  
Virus Release ◽  
Immunodeficiency Virus ◽  
Ptap Motif ◽  
Hiv 1

ABSTRACT Late (L) domains are required for the efficient release of several groups of enveloped viruses. Three amino acid motifs have been shown to provide L-domain function, namely, PPXY, PT/SAP, or YPDL. The retrovirus Mason-Pfizer monkey virus (MPMV) carries closely spaced PPPY and PSAP motifs. Mutation of the PPPY motif results in a complete loss of virus release. Here, we show that the PSAP motif acts as an additional L domain and promotes the efficient release of MPMV but requires an intact PPPY motif to perform its function. Examination of HeLaP4 cells expressing PSAP mutant virus by electron microscopy revealed mostly late budding structures and chains of viruses accumulating at the cell surface with little free virus. In the case of the PPPY mutant virus, budding appeared to be mostly arrested at an earlier stage before induction of membrane curvature. The cellular protein TSG101, which interacts with the human immunodeficiency virus type 1 (HIV-1) PTAP L domain, was packaged into MPMV in a PSAP-dependent manner. Since TSG101 is crucial for HIV-1 release, this result suggests that the Gag-TSG101 interaction is responsible for the virus release function of the MPMV PSAP motif. Nedd4, which has been shown to interact with viral PPPY motifs, was also detected in MPMV particles, albeit at much lower levels. Consistent with a role of VPS4A in the budding of both PPPY and PTAP motif-containing viruses, the overexpression of ATPase-defective GFP-VPS4A fusion proteins blocked both wild-type and PSAP mutant virus release.

scholarly journals Essential Role of Plasminogen Activator Inhibitor Type-1 in Radiation Enteropathy

2008 ◽  
Vol 172 (3) ◽  
pp. 691-701 ◽  
Author(s):  
Fabien Milliat ◽  
Jean-Christophe Sabourin ◽  
Georges Tarlet ◽  
Valerie Holler ◽  
Eric Deutsch ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Essential Role ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor Type ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor
Sign in / Sign up

Export Citation Format

Share Document