Oncogenic transformation adenovirus e1a proteins. Medical search. Frequent questions

The first is lytic infection, which occurs when an adenovirus enters human epithelial cells and continues through an entire replication cycle, which results in cytolysis, cytokine production, and induction of host inflammatory response. (medscape.com)
To address this and to also study the oncogenic potential of unregulated function of dominant regulators of epithelial homeostasis noted above, we developed Multi-Functional Human Tissue Genetics noted above which, when combined with skin tissue regeneration on immune deficient mice, has permitted the molecular reconstruction of events sufficient to trigger human cancer. (stanford.edu)

HPV is present in cervical cancer, where it expresses the oncogenic proteins E6 and E7 that inactivate the host regulatory proteins p53 and RB, respectively. (sv40.org)
The effects of miR2911 on endogenous E6/E7 mRNA and protein levels were detected in HPV16/18-positive cervical cancer cells by RT-qPCR and Western blotting. (bvsalud.org)
In addition, the endogenous E6/E7 mRNA and protein levels were significantly decreased by using miR2911 treatment in HPV16/18-positive cervical cancer cells. (bvsalud.org)

The genome of adenovirus is well known and can be modified with relative ease to induce lysis or cytotoxicity of a specified cell line without affecting others. (medscape.com)

Adenovirus is known to be oncogenic in rodents but not in humans. (medscape.com)
C-terminal-binding protein 2 also known as CtBP2 is a protein that in humans is encoded by the CTBP2 gene. (wikipedia.org)

Upon infection with adenovirus, one of three different interactions with the cells may occur. (medscape.com)
Wild-type p110α has more interactions with the nSH2 domain than the oncogenic mutant H1047R. (oncotarget.com)

Of interest is the role of adenoviruses as viral vectors in vaccination and in gene therapy.For example, in viral vector vaccines against SARS-CoV2, the vector virus is used to deliver RNA encoding SARS-CoV2 spike protein into target cells. (medscape.com)
They appear to be primarily scaffold proteins that allow the assembly of gene repression complexes. (wikipedia.org)
The mammalian CtBP2 gene produces alternative transcripts encoding two distinct proteins. (wikipedia.org)
In the vertebrate retina, the CtBP2 gene is transcribed from alternative promoters during retinal development yielding the CTBP2 transcriptional coregulator as well as the larger ribbon synapse scaffolding protein RIBEYE. (wikipedia.org)
These data show that tumor induction by adenovirus virions is not determined only by the gene products of the transforming region. (uu.nl)

Similarly, the early lethality of the CtBP2 knockout and of double knockout mice has precluded detailed analysis of the cellular effects of deleting these proteins. (wikipedia.org)
We showed that HPV-positive HNC cells presented a transcriptional and functional impairment of the autophagic process compared to HPV-negative cells, which were reactivated by knocking down HPV E6/E7 oncoproteins, the drivers of cellular transformation. (bvsalud.org)

Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. (wikipedia.org)

Adenovirus, a DNA virus, was first isolated in the 1950s in adenoid tissue-derived cell cultures, hence the name. (medscape.com)
An extremely hardy virus, adenovirus is ubiquitous in human and animal populations, survives long periods outside a host, and is endemic throughout the year. (medscape.com)
We have constructed a nondefective recombinant virus between the nononcogenic adenovirus 5 (Ad5) and the highly oncogenic Ad12. (uu.nl)
Thus, despite the fact that all products required for oncogenic transformation in vitro were derived from the highly oncogenic Ad12, the recombinant virus did not produce tumors in vivo. (uu.nl)
efficient and reliable establishment of lymphoblastoid cell lines by epstein-barr virus transformation from a limited amount of peripheral blood. (liverpool.ac.uk)

These models are being used to systematically elucidate proteins required for cutaneous carcinogenesis and to test their potential role as therapeutic targets. (stanford.edu)

Homeodomain-interacting protein kinases (HIPKs) belong to the CMGC kinase family and are closely related to dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs). (nature.com)
Homeodomain-interacting protein kinases (HIPKs) are an evolutionarily conserved kinase family comprising the members HIPK1, HIPK2, and HIPK3 in vertebrates, and, additionally, HIPK4 in mammals. (nature.com)

Recovery from adenovirus infection is associated with the development of serotype-specific neutralizing antibodies. (medscape.com)

20. Use of adenoviral E1A protein to analyze K18 promoter deregulation in colon carcinoma cells discloses a role for CtBP1 and BRCA1. (nih.gov)
In a yeast two-hybrid screen we have identified Sprouty1 (Spry1) as a target of adenoviral E1A Oncoproteins. (biomedcentral.com)
The team focused on an adenoviral oncogene called E1A, and a protein that it codes for with the same name. (vetscite.org)

The first is lytic infection, which occurs when an adenovirus enters human epithelial cells and continues through an entire replication cycle, which results in cytolysis, cytokine production, and induction of host inflammatory response. (medscape.com)
7. Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection. (nih.gov)

One important question is whether the membrane protein needs links to cytoskeletal proteins to function as a motor as the model predicts. (nih.gov)
AN - coordinate IM with ADENOMA (IM) HN - 2006 BX - Corticotroph Adenoma BX - Pituitary Adenoma, ACTH-Secreting BX - Pituitary Corticotropin-Secreting Adenoma MH - Actin Capping Proteins UI - D051344 MN - D5.750.78.730.32 MN - D12.776.220.525.32 MS - Actin capping proteins are cytoskeletal proteins that bind to the ends of ACTIN FILAMENTS to regulate actin polymerization. (nih.gov)

In the vertebrate retina, the CtBP2 gene is transcribed from alternative promoters during retinal development yielding the CTBP2 transcriptional coregulator as well as the larger ribbon synapse scaffolding protein RIBEYE. (wikipedia.org)
1. Inhibition of transcriptional activation and cell proliferation activities of adenovirus E1A by the unique N-terminal domain of CtBP2. (nih.gov)
2. Changes in C-terminal binding protein 2 (CtBP2) corepressor complex induced by E1A and modulation of E1A transcriptional activity by CtBP2. (nih.gov)
4. PLDLS-dependent interaction of E1A with CtBP: regulation of CtBP nuclear localization and transcriptional functions. (nih.gov)
5. Roles of p300, pocket proteins, and hTBP in E1A-mediated transcriptional regulation and inhibition of p53 transactivation activity. (nih.gov)
C-terminal binding protein 1 (CtBP1), a transcriptional corepressor that regulates the expression of tumor suppressors and genes involved in cell death, is known to play a role in multiple cancers. (nih.gov)
20 Through its N-terminal hydrophobic domain, NPM also exerts a chaperone activity, preventing protein aggregation in the nucleolus, favoring histone and nucleosome assembly, 21 - 23 and increasing acetylation-dependent transcriptional activity. (haematologica.org)

The full functional roles of CtBP proteins in mammals have been difficult to evaluate because of partial redundancy between CtBP1 and CtBP2. (wikipedia.org)
12. A novel C-terminal binding protein (CTBP2) is closely related to CTBP1, an adenovirus E1A-binding protein, and maps to human chromosome 21q21.3. (nih.gov)

Spry proteins are central and complex regulators of the receptor tyrosine kinase (RTK) signalling pathway. (biomedcentral.com)
It is known that the human Ras GTPase activating protein (GAP) p120-GAP can be phosphorylated by different members of the Src kinase family and recently phosphorylation of the GDP/GTP exchange factor (GEF) CDC25Mm/GRF1 by proteins of the Src kinase family has been revealed in vivo [Kiyono, M., Kaziro, Y. & Satoh, T. (2000) J. Biol. (embl.de)
In addition to its association with Ras, GAP has been shown to bind to several tyrosine-phosphorylated proteins in cells stimulated by growth factors or expressing transforming tyrosine kinase variants. (embl.de)
Association of Human Cyclin E with a Periodic G.sub.1 -S Phase Protein Kinase", Science 257:1958-1961 (1992). (everypatent.com)
Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. (lookformedical.com)
for example, protein kinase activation is part of the platelet activation signal pathway. (lookformedical.com)

18. Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region. (nih.gov)
So konnte mit dem POD-assoziierten Transkriptionskoaktivator p300 erstmals ein zellulärer Interaktionspartner von E4orf3 identifiziert werden, der auch ein Zielprotein der E1A-Onkoproteine darstellt. (uni-regensburg.de)
Immunfluoreszenz- und funktionelle Promotor/Reporter-Analysen zeigen, dass das Ad5-Protein p300 in reorganisierte POD-Strukturen sequestriert und die transkriptionsaktiven Eigenschaften des Tumorsuppressorproteins inhibiert. (uni-regensburg.de)
Da auch die E1A-Proteine die p300-vermittelte Transkriptionsaktivierung blockieren, muss man annehmen, dass E4orf3 mit E1A redundante Aktivitäten aufweist. (uni-regensburg.de)
Dafür spricht auch die Beobachtung, dass die Binderegionen von E1A und E4orf3 im p300-Protein teilweise überlappen und die Tatsache, dass das Ad5 E4orf3-Protein eine p300-bindungsdefiziente, transformationsdefekte E1A-Mutante (E1delN) in BRK-Transformationsexperimenten komplementiert. (uni-regensburg.de)
Insgesamt zeigen diese Ergebnisse, dass die E4orf3-Proteine humaner Adenoviren eine zu E1A redundante Funktion besitzen und lassen vermuten, dass die onkogenen und mutagenen Eigenschaften des Ad5-Proteins über die Modulation der subnukleären Lokalisation und Funktion von p300 vermittelt werden. (uni-regensburg.de)

expression of these proteins is maintained in carcinoma cells lines [6], and expression of these two proteins induces immortalization and transformation in a variety of rodent and human cell types [54]. (nih.gov)

These primary cell cultures were often noted to spontaneously degenerate over time, and adenoviruses are now known to be a common cause of asymptomatic respiratory tract infection that produces in vitro cytolysis in these tissues. (medscape.com)
Adenovirus is often cultured from the pharynx and stool of asymptomatic children, and most adults have measurable titers of anti-adenovirus antibodies, implying prior infection. (medscape.com)
Recovery from adenovirus infection is associated with the development of serotype-specific neutralizing antibodies. (medscape.com)
Upon infection with adenovirus, one of three different interactions with the cells may occur. (medscape.com)
Changes in the activity of DNA repair proteins during viral infection can cause disturbances in the DNA repair system and change its mechanisms. (springer.com)
Only several of those studies report some evidence of increased cell repair capacity after infection or viral protein overexpression (Chipitsyna et al. (springer.com)
These structures, which are round in the uninfected cell, dissolve after adenovirus infection and form elongated fibrils. (mhh.de)
Hofmann S , Stubbe M, Mai J, Schreiner S. 2021.Double-edged Role of PML Nuclear Bodies during Human Adenovirus Infection. (mhh.de)

Human cytomegalovirus (HCMV) is a member of the betaherpesvirus subfamily and encodes more than 200 viral proteins (Chee et al. (springer.com)

Possessing over60 serotypes, adenovirus is recognized as the etiologic agent of various diverse syndromes. (medscape.com)
CR3 is one of four E1A regions (CR1, CR2, CR3 and CR4) that are highly conserved among all Adenovirus serotypes [ 2 ]. (biomedcentral.com)

15. Modulation of oncogenic transformation by the human adenovirus E1A C-terminal region. (nih.gov)

E1A oncoproteins cooperate with Ad early region 1B (E1B) oncogene products to transform rodent cells in culture and, depending on the serotype, to induce tumors in immunocompetent animals (e.g. (biomedcentral.com)

Several of these properties are shared with other viral oncoproteins, specifically adenovirus E1A and SV40 large T antigen, with which E7 shares extensive sequence similarity in certain regions identified with these biological properties. (nih.gov)
Figures 2 and 3 illustrate sequence similarities between the E7 proteins of various HPV types, and similarities between the E7 protein and other viral oncoproteins, respectively. (nih.gov)

The accessory GTPase-activating proteins (GAPs) negatively regulate the cell signaling by increasing the slow intrinsic GTP to GDP hydrolysis rate of Ras. (embl.de)

16. Expression of CtBP family protein isoforms in breast cancer and their role in chemoresistance. (nih.gov)
We also demonstrated the interaction of E1A with two further Spry isoforms. (biomedcentral.com)

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. (lookformedical.com)

Using deletion mutants we identified the N-terminus and the CR conserved region (CR) 3 of E1A- and the C-terminal half of Spry1, which contains the highly conserved Spry domain, as the essential sites for direct interaction between Spry and E1A. (biomedcentral.com)
All known oncogenic mutants of Ras map to a small subset of amino acids. (embl.de)

The N terminus and the CRs of E1A mediate most of the gene regulatory functions necessary for viral reproduction and transformation [ 8 ]. (biomedcentral.com)

Adenovirus carries a number of cooperating genes that modulate cell growth in ways we're interested in," said William Tansey, Ph.D., who, along with CSHL professors Scott Lowe, Ph.D., and Gregory Hannon, Ph.D., is one of the team's co-leaders and corresponding author of a paper in Proceedings of the National Academy of Sciences. (vetscite.org)
Our results suggest that phosphorylation by p60c-Src and Lck is a selective process that can modulate the activity of p120-GAP and CDC25Mm towards Ras proteins. (embl.de)

3. Interaction of ZEB and histone deacetylase with the PLDLS-binding cleft region of monomeric C-terminal binding protein 2. (nih.gov)
Here, we confirm our yeast two-hybrid data, showing the interaction between Spry1 and E1A in GST pull-down and immunoprecipitation assays. (biomedcentral.com)

The CtBPs bind to many different DNA-binding proteins and also bind to co-repressors that are themselves bound to DNA-binding proteins, such as Friend of GATA (Fog). (wikipedia.org)
Coupled to the outside are "protein arms" that bind short RNA helices and embed them. (vetscite.org)

They do this by binding to sequence-specific DNA-binding proteins that carry a short motif of the general form Proline-Isoleucine-Aspartate-Leucine-Serine (the PIDLS motif). (wikipedia.org)

6. Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins. (nih.gov)

Initiation of adenovirus DNA replication in vitro requires a specific DNA sequence. (nih.gov)
The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. (nih.gov)

Within this research program, we are investigating how the virus reproduces in the cell with a special focus on marked changes in what are called PML nuclear complexes made up of several proteins within the cell. (mhh.de)

The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. (nih.gov)
Arp2-3 complex binds WASP PROTEIN and existing ACTIN FILAMENTS, and it nucleates the formation of new branch point filaments. (nih.gov)
HN - 2006 BX - Arp2-3 Complex MH - Actin-Related Protein 3 UI - D051378 MN - D5.750.78.730.246.750 MN - D12.776.220.525.246.750 MS - A component of the Arp2-3 complex that is related in sequence and structure to ACTIN and that binds ATP. (nih.gov)

The idea that E1A is also capable of exerting its regulatory functions by directly affecting cytoplasmic processes was supported by the discovery that a certain amount of E1A proteins is acetylated at Lys 239 , which determines the cytoplasmic localization of E1A proteins by interfering with the nuclear transport [ 13 ]. (biomedcentral.com)
Identification of a nuclear polypeptide (cyclin) whose relative proportion is sensitive to changes in the rate of cell proliferation and to transformation", Prog. (everypatent.com)
Cyclin: A Nuclear Protein Whose Level Correlates Directly with the Proliferative State of Normal As Well as Transformed Cells", Leukemia Res. (everypatent.com)

NPM is over-expressed in solid tumors of diverse histological origin 6 or is involved in tumor progression 7 - 9 In several hematologic malignancies, the NPM1 locus is lost 10 or translocated leading to the formation of oncogenic fusion proteins. (haematologica.org)

An extremely hardy virus, adenovirus is ubiquitous in human and animal populations, survives long periods outside a host, and is endemic throughout the year. (medscape.com)
The transforming potential of human adenoviruses has been traditionally ascribed to the E1A and E1B transcription units encoded within early region 1 (E1). (uni-regensburg.de)
Prions, rogue proteins that cause incurable brain infections such as Mad Cow disease and its human equivalent, variant Creutzfeldt-Jakob Disease, are difficult to inactivate, resisting extreme heat, chemical disinfectants, and irradiation. (vetscite.org)
Human adenoviruses cause conjunctivitis, gastrointestinal illnesses and pneumonia, among other things. (mhh.de)

The protein ribbons organized themselves into a defined threadlike double layer that sets the shape and size. (vetscite.org)

Immunofluorescent microscopy data revealed a co-localization of E1A 13S with Spry1 in the cytoplasm. (biomedcentral.com)

Altered expression of cyclins, such as overproduction of cyclins, particularly cyclin E, or production of alternative cyclin E proteins, as well as deranged appearance of mitotic cyclins during the cell cycle, are indicative of the presence of carcinoma. (everypatent.com)

Adenovirus has been associated with both sporadic and epidemic disease and, with regard to infections among military recruits, who were routinely immunized against types 4 and 7 from 1971 until the cessation of vaccine production in 1996. (medscape.com)

Regulates E3 ubiquitin-protein ligase activity of RNF19A (By similarity). (nih.gov)

17. Identification of a second CtBP binding site in adenovirus type 5 E1A conserved region 3. (nih.gov)

Proteins encoded by the early transcription unit 1A (E1A) of Adenovirus (Ad) are essential for the viral life cycle because of their necessity in regulating the expression of all other viral genes [ 1 ]. (biomedcentral.com)
The team's findings are the latest in a long and distinguished line of research at CSHL involving adenovirus, a type of virus that causes the common cold in people, but whose genome contains known oncogenes - genes whose expression can promote cancer under certain conditions. (vetscite.org)

Image reconstruction reveals the complex molecular organization of adenovirus. (nih.gov)
Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. (nih.gov)
HN - 2006(1998) MH - Actin-Related Protein 2-3 Complex UI - D051376 MN - D5.750.78.730.246 MN - D12.776.220.525.246 MS - A complex of seven proteins including ARP2 PROTEIN and ARP3 PROTEIN that plays an essential role in maintenance and assembly of the CYTOSKELETON. (nih.gov)

Point mutations and deletions have been used to map the contribution of particular elements of the protein sequence to a given function. (nih.gov)

14 B23.1, the prevalent isoform in all tissues, 15 contains 294 amino acids, 16 whereas B23.2, a truncated protein, lacks the last 35 C-terminal amino acids of B23.1 and is expressed at very low levels. (haematologica.org)

Recently we and others have shown that two additional proteins of early region 4 (Ad5 E4orf6 and E4orf3) possess transforming and oncogenic potential. (uni-regensburg.de)

Die in der vorliegenden Arbeit dargestellten Untersuchungen zum transformierenden Potenzial humaner Adenoviren zeigen erstmals, dass zwei virale Genprodukte der frühen Region 4 - E4orf3 und E4orf6 - von Adenovirus Serotyp 5 transformierende Eigenschaften aufweisen, die zur 'Hit & Run'-Transformation primärer BRK-Zellen beitragen. (uni-regensburg.de)

Anatomy21

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Phenomena and Processes75

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Gene5

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