scholarly journals Cellular Functions of HPV16 E5 Oncoprotein during Oncogenic Transformation

Author(s):  
Lourdes Gutierrez-Xicotencatl ◽  
Adolfo Pedroza-Saavedra ◽  
Lilia Chihu-Amparan ◽  
Azucena Salazar-Piña ◽  
Minerva Maldonado-Gama ◽  
...  
2008 ◽  
Vol 18 (3) ◽  
pp. 534-539
Author(s):  
C. X CAO ◽  
J. MA ◽  
M. XUN ◽  
X. XUE ◽  
P. CHEN ◽  
...  

The novel human oncogenehWAPLis associated with uterine cervical cancer. The HPV16 E5 oncoprotein could induce genomic instability in normal human cells. However, the mechanism of E5 interaction with hWAPL still awaits definition. In our present studies, the eukaryotic expression plasmids, pcDNA3-hWAPL and pcDNA3-hWAPL-E5 were constructed and carried out to vaccinate mice directly. The result that indicated the polyclonal antibody titer in immunized mice sera was increased by enzyme-linked immunosorbent assay. In addition, the proliferative responses of immunized mice spleen cells showed the optical densities values in vaccinated group remarkably higher than that in the control group. In conclusion, the recombinant plasmids could induce strong humoral and cellular immune response and exhibited great potential as therapeutic targets in the treatment of cervical cancer. However, the result didn't show significant difference in group with coexpression of HPV16 E5–hWAPL and group with only hWAPL expression. Consistent with these observations, we demonstrated that HPV16 E5 was not the optimal factor to cooperate with hWAPL in gene therapy.


2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Matthew L. Scott ◽  
Brittany L. Woodby ◽  
Joseph Ulicny ◽  
Gaurav Raikhy ◽  
A. Wayne Orr ◽  
...  

ABSTRACT Human papillomaviruses (HPVs) infect keratinocytes of stratified epithelia. Long-term persistence of infection is a critical risk factor for the development of HPV-induced malignancies. Through the actions of its oncogenes, HPV evades host immune responses to facilitate its productive life cycle. In this work, we discovered a previously unknown function of the HPV16 E5 oncoprotein in the suppression of interferon (IFN) responses. This suppression is focused on keratinocyte-specific IFN-κ and is mediated through E5-induced changes in growth factor signaling pathways, as identified through phosphoproteomics analysis. The loss of E5 in keratinocytes maintaining the complete HPV16 genome results in the derepression of IFNK transcription and subsequent JAK/STAT-dependent upregulation of several IFN-stimulated genes (ISGs) at both the mRNA and protein levels. We also established a link between the loss of E5 and the subsequent loss of genome maintenance and stability, resulting in increased genome integration. IMPORTANCE Persistent human papillomavirus infections can cause a variety of significant cancers. The ability of HPV to persist depends on evasion of the host immune system. In this study, we show that the HPV16 E5 protein can suppress an important aspect of the host immune response. In addition, we find that the E5 protein is important for helping the virus avoid integration into the host genome, which is a frequent step along the pathway to cancer development.


Author(s):  
Robert M. Glaeser ◽  
Thea B. Scott

The carbon-replica technique can be used to obtain information about cell-surface structure that cannot ordinarily be obtained by thin-section techniques. Mammalian erythrocytes have been studied by the replica technique and they appear to be characterized by a pebbly or “plaqued“ surface texture. The characteristic “particle” diameter is about 200 Å to 400 Å. We have now extended our observations on cell-surface structure to chicken and frog erythrocytes, which possess a broad range of cellular functions, and to normal rat lymphocytes and mouse ascites tumor cells, which are capable of cell division. In these experiments fresh cells were washed in Eagle's Minimum Essential Medium Salt Solution (for suspension cultures) and one volume of a 10% cell suspension was added to one volume of 2% OsO4 or 5% gluteraldehyde in 0.067 M phosphate buffer, pH 7.3. Carbon replicas were obtained by a technique similar to that employed by Glaeser et al. Figure 1 shows an electron micrograph of a carbon replica made from a chicken erythrocyte, and Figure 2 shows an enlarged portion of the same cell.


Author(s):  
D. L. Taylor

Cells function through the complex temporal and spatial interplay of ions, metabolites, macromolecules and macromolecular assemblies. Biochemical approaches allow the investigator to define the components and the solution chemical reactions that might be involved in cellular functions. Static structural methods can yield information concerning the 2- and 3-D organization of known and unknown cellular constituents. Genetic and molecular techniques are powerful approaches that can alter specific functions through the manipulation of gene products and thus identify necessary components and sequences of molecular events. However, full knowledge of the mechanism of particular cell functions will require direct measurement of the interplay of cellular constituents. Therefore, there has been a need to develop methods that can yield chemical and molecular information in time and space in living cells, while allowing the integration of information from biochemical, molecular and genetic approaches at the cellular level.


Author(s):  
John C. Garancis ◽  
Robert O. Hussa ◽  
Michael T. Story ◽  
Donald Yorde ◽  
Roland A. Pattillo

Human malignant trophoblast cells in continuous culture were incubated for 3 days in medium containing 1 mM N6-O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) and 1 mM theophylline. The culture fluid was replenished daily. Stimulated cultures secreted many times more chorionic gonadotropin and estrogens than did control cultures in the absence of increased cellular proliferation. Scanning electron microscopy revealed remarkable surface changes of stimulated cells. Control cells (not stimulated) were smooth or provided with varying numbers of microvilli (Fig. 1). The latter, usually, were short and thin. The surface features of stimulated cells were considerably different. There was marked increase of microvilli which appeared elongated and thick. Many cells were covered with confluent polypoid projections (Fig. 2). Transmission electron microscopy demonstrated marked activity of cytoplasmic organelles. Mitochondria were increased in number and size; some giant forms with numerous cristae were observed.


2020 ◽  
Vol 48 (2) ◽  
pp. 613-620
Author(s):  
Clara Ortegón Salas ◽  
Katharina Schneider ◽  
Christopher Horst Lillig ◽  
Manuela Gellert

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.


2013 ◽  
Vol 51 (01) ◽  
Author(s):  
D Dauch ◽  
T Wuestefeld ◽  
TW Kang ◽  
R Rudalska ◽  
A Hohmeyer ◽  
...  

1987 ◽  
Vol 58 (03) ◽  
pp. 936-942 ◽  
Author(s):  
Lindsey A Miles ◽  
Edward F Plow

SummaryGlu-plasminogen binds to platelets; the monocytoid line, U937, and the human fetal fibroblast line, GM1380 bind both plasminogen and its activator, urokinase. This study assesses the interaction of these fibrinolytic proteins with circulating human blood cells. Plasminogen bound minimally to red cells but bound saturably and reversibly to monocytes, granulocytes and lymphocytes with apparent Kd values of 0.9-1.4 μM. The interactions were of high capacity with 1.6 to 49 × 105 sites/cell and involved the lysine binding sites of plasminogen. Both T cells and non-rosetting lymphocytes and two B cell lines saturably bound plasminogen. Urokinase bound saturably to gianulocytes, monocytes, non-rosetting lymphocytes and a B cell line, but minimally to T cells, platelets and red cells. Therefore, plasminogen binding sites of high capacity, of similar affinities, and with common recognition specificities are expressed by many peripheral blood cells. Urokinase receptors are also widely distributed, but less so than plasminogen binding sites. The binding ol plasminogen and/ or urokinase to these cells may lead to generation of cell- associated proteolytic activity which contributes to a variety of cellular functions.


1989 ◽  
Vol 120 (3_Suppl) ◽  
pp. S194
Author(s):  
B. E. WENZEL ◽  
A. HEUFELDER ◽  
T. MACKENROTH ◽  
P. C. SCRIBA

2007 ◽  
Vol 49 (4) ◽  
pp. 244-258
Author(s):  
Takashi Kanematsu ◽  
Akiko Mizokami ◽  
Miho Terunuma ◽  
Hiroshi Takeuchi ◽  
Masato Hirata

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