Molecular regulation and biological function of adenovirus early genes: The E4 ORFs

Gene

Volumn 278, Issue 1-2, 2001, Pages 1-23

  Täuber, Birgitt ^a   Dobner, Thomas ^a  

^a UNIVERSITY HOSPITAL REGENSBURG   (Germany)

Author keywords

DNA tumor virus; Gene therapy; Lytic infection; Transformation

Indexed keywords

GENE PRODUCT; PROTEIN E4; UNCLASSIFIED DRUG; VIRUS PROTEIN; VIRUS VECTOR;

ADENOVIRUS; APOPTOSIS; ARTICLE; CARCINOGENESIS; CELL CYCLE; CELL NUCLEUS INCLUSION BODY; CYTOTOXICITY; DNA REPAIR; GENE FUNCTION; GENE THERAPY; GENETIC TRANSCRIPTION; HOST CELL; IMMUNE RESPONSE; MAMMAL CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTERACTION; REGULATORY MECHANISM; VIROGENESIS; VIRUS GENE; VIRUS INFECTION; VIRUS ONCOGENE; VIRUS REPLICATION;

EID: 0035980625     PISSN: 03781119     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0378-1119(01)00722-3     Document Type: Review

References (224)

1. Selection of apoptosis-deficient adenovirus E4orf4 mutants in Saccharomyces cerevisiae
2. Proteins with transcription regulatory properties encoded by human adenoviruses
3. Replicative adenoviruses for cancer therapy
4. Adenovirus type 9-induced tumorigenesis in the rat mammary gland related to sex hormonal state
5. Induction of mammary fibroadenomas in rats by adenovirus type 9
6. Effect of the E4 region on the persistence of transgene expression from adenovirus vectors
7. E4ORF3 requirement for achieving long-term transgene expression from the cytomegalovirus promoter in adenovirus vectors
8. Adenovirus E1B proteins are required for accumulation of late viral mRNA and for effects on cellular mRNA translation and transport
9. Functional synergy between DP-1 and E2F-1 in the cell cycle-regulating transcription factor DRTF1/E2F
10. Adenovirus vectors for gene delivery
11. Oncogenicity by adenovirus is not determined by the transforming region only
12. Analysis of synthesis, stability, phosphorylation, and interacting polypeptides of the 34-kilodalton product of open reading frame 6 of the early region 4 protein of human adenovirus type 5
13. The carboxy-terminal exon of the adenovirus E1A protein is required for E4F-dependent transcription activation
14. Adenovirus E4 open reading frame 4 protein autoregulates E4 transcription by inhibiting E1A transactivation of the E4 promoter
15. Genetic analysis of a potential zinc-binding domain of the adenovirus E4 34k protein
16. Adenovirus E4 34k and E4 11k inhibit double strand break repair and are physically associated with the cellular DNA-dependent protein kinase
17. Identification and peptide mapping of human adenovirus type 2-induced early polypeptides isolated by two-dimensional gel electrophoresis and immunoprecipitation
18. Induction of apoptosis and G2/M arrest by infection with replication-deficient adenovirus at high multiplicity of infection
19. Redundant control of adenovirus late gene expression by early region 4
20. Interaction of adenoviral E4 and E1b products in late gene expression
21. Adenovirus early region 4 and viral DNA synthesis
22. Letter to the editor
23. Activation of transgene expression by early region 4 is responsible for a high level of persistent transgene expression from adenovirus vectors in vivo
24. Structure of the adenovirus E4 Orf6 protein predicted by fold recognition and comparative protein modeling
25. p53 is a general repressor of RNA polymerase III transcription
26. Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies
27. A functional complex of the adenovirus proteins E1B-55kDa and E4orf6 is necessary to modulate the expression level of p53 but not its transcriptional activity
28. Transcriptional activation by the adenovirus larger E1a product is mediated by members of the cellular transcription factor ATF family which can directly associate with E1a
29. The complete DNA sequence and genomic organization of the avian adenovirus CELO
30. Role of E4 in eliciting CD4 T-cell and B-cell responses to adenovirus vectors delivered to murine and nonhuman primate lungs
31. Modulation of the inflammatory properties and hepatotoxicity of recombinant adenovirus vectors by the viral E4 gene products
32. A role for a bent DNA structure in E2F-mediated transcription activation
33. Use of the E2F transcription factor by DNA tumor virus regulatory proteins
34. Analysis of adenovirus early region 4-encoded polypeptides synthesized in productively infected cells
35. The DNA sequence of adenovirus type 40
36. Long-term gene delivery into the livers of immunocompetent mice with E1/E4-defective adenoviruses
37. Regulated splicing of adenovirus type 5 E4 transcripts and regulated cytoplasmic accumulation of E4 mRNA
38. Expression of adenovirus type 5 E4 Orf2 protein during lytic infection
39. Does the antitumor adenovirus ONYX-015/dl1520 selectively target cells defective in the p53 pathway?
40. Nuclear export of the E1B 55-kDa and E4 34-kDa adenoviral oncoproteins mediated by a rev-like signal sequence
41. Letter to the editor
42. Nuclear export of adenovirus RNA
43. Blockage by adenovirus E4orf6 of transcriptional activation by the p53 tumor suppressor
44. The adenovirus type 5 E1B-55K oncoprotein actively shuttles in virus-infected cells, whereas transport of E4orf6 is mediated by a CRM1 independent-mechanism
45. Adenovirus replication is coupled with the dynamic properties of the PML nuclear structure
46. The promyelocytic (PML) nuclear compartment and transcriptional control
47. Mapping of a 14,000-dalton antigen to early region 4 of the human adenovirus 5 genome
48. Formation of adeno-associated virus circular genomes is differentially regulated by adenovirus E4 ORF6 and E2a gene expression
49. In vitro translation of adenovirus type 12-specific mRNA isolated from infected and transformed cells
50. Viral gene products in adenovirus type 2-transformed hamster cells
51. Expression of early viral gene products in adenovirus type 12-infected and -transformed cells
52. pRB binds to and modulates the transrepressing activity of the E1A- regulated transcription factor p120E4F
53. Adenovirus early region 4 is required for efficient virus particle assembly
54. PDZ domains: Fundamental building blocks in the organization of protein complexes at the plasma membrane
55. The adenovirus E1A-regulated transcription factor E4F is generated from the human homolog of nuclear factor phiAP3
56. Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors
57. Control of adenovirus early gene expression during the late phase of infection
58. E2F-1 functions in mice to promote apoptosis and suppress proliferation
59. A potential NES of the Epstein-Barr virus nuclear antigen 1 (EBNA1) does not confer shuttling
60. Transduction with recombinant adeno-associated virus for gene therapy is limited by leading-strand synthesis
61. Adenovirus transcription. V. Quantitation of viral RNA sequences in adenovirus 2-infected and transformed cells
62. Viral transactivating proteins
63. Comparison of viral RNA sequences in adenovirus 2-transformed and lytically infected cells
64. Viral nucleic acid sequences in transformed cells. IV. A study of the sequences of adenovirus 5 DNA and RNA in four lines of adenovirus 5-transformed rodent cells using specific fragments of the viral genome
65. Regulation of p53 activity in nuclear bodies by a specific PML isoform
66. Characterization of the major mRNAs from adenovirus 2 early region 4 by cDNA cloning and sequencing
67. Biology of adenovirus vectors with E1 and E4 deletions for liver-directed gene therapy
68. Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation
69. The E4 promoter of adenovirus type 2 contains an E1A dependent cis-acting element
70. Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high- risk papillomavirus E6 oncoproteins
71. p53 status does not determine outcome of E1B 55-Kilodalton mutant adenovirus lytic infection
72. Roles for the E4 orf6, orf3, and E1B 55-kilodalton proteins in cell cycle-independent adenovirus replication
73. Adenovirus early region 4 34-kilodalton protein directs the nuclear localization of the early region 1B 55-kilodalton protein in primate cells
74. Generation of an adenovirus vector lacking E1, E2a, E3, and all of E4 except open reading frame 3
75. Transformation by and oncogenicity of human adenoviruses
76. Enhanced expression of p53 in human cells infected with mutant adenoviruses
77. Differential influence of the E4 adenoviral genes on viral and cellular promoters
78. Overexpression of cyclin A inhibits augmentation of recombinant adeno- associated virus transduction by the adenovirus E4orf6 protein
79. Adenovirus early region 4 encodes functions required for efficient DNA replication, late gene expression, and host cell shutoff
80. Inhibition of adenovirus early region IV transcription in vitro by a purified viral DNA binding protein
81. p53-independent and -dependent requirements for E1B-55k in adenovirus type 5 replication
82. E2F from adenovirus-infected cells binds cooperatively to DNA containing two properly oriented and spaced recognition sites
83. An adenovirus early region 4 gene product is required for induction of the infection-specific form of cellular E2F activity
84. Heterodimerization of the transcription factors E2F-1 and DP-1 is required for binding to the adenovirus E4 (ORF6/7) protein
85. Nucleotide sequence of adenovirus 2 DNA fragment encoding for the carboxylic region of the fiber protein and the entire E4 region
86. Adenovirus E4orf6 oncoprotein modulates the function of the p53-related protein, p73
87. RNA-binding activity of the E1B 55-kilodalton protein from human adenovirus type 5
88. Adenoviruses
89. Adenovirus early region 4 encodes two gene products with redundant effects in lytic infection
90. The adenovirus early region 4 open reading frame 6/7 protein regulates the DNA binding activity of the cellular transcription factor, E2F, through a direct complex
91. Post-transcriptional control of adenovirus gene expression
92. The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition
93. Human adenovirus type 9-induced rat mammary tumors
94. Requirement for the adenovirus type 9 E4 region in production of mammary tumors
95. Adenovirus type 9 E4 open reading frame 1 encodes a transforming protein required for the production of mammary tumors in rats
96. Mammary tumors induced by human adenovirus type 9: A role for the viral early region 4 gene
97. Oncogenic capacity of the E2F1 gene
98. E1A-mediated activation of the adenovirus E4 promoter can occur independently of the cellular transcription factor E4F
99. Regulation of adenovirus alternative RNA splicing by dephosphorylation of SR proteins
100. Novel role for E4 region genes in protection of adenovirus vectors from lysis by cytotoxic T lymphocytes
101. Computer-assisted identification of cell cycle-regulated genes: New targets for E2F transcription factors
102. Mutations in the adenovirus-encoded single-stranded DNA binding protein that result in altered accumulation of early and late viral RNAs
103. Adenovirus E4orf4 protein binds to protein phosphatase 2A, and the complex down regulates E1A-enhanced junB transcription
104. Induction of apoptosis by adenovirus E4orf4 protein
105. Adenovirus E4orf4 protein induces PP2A-dependent growth arrest in Saccharomyces cerevisiae and interacts with the anaphase-promoting complex/cyclosome
106. Identification of a cellular transcription factor involved in E1A trans-activation
107. E1A transcription induction: Enhanced binding of a factor to upstream promoter sequences
108. Role of an adenovirus E2 promoter binding factor in E1A-mediated coordinate gene control
109. The adenovirus type 5 E1B-55k oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2
110. Adenovirus type 5 E4orf3 protein relieves p53 inhibition by E1B-55-kilodalton protein
111. E4orf4, a novel adenovirus death factor that induces p53-independent apoptosis by a pathway that is not inhibited by zVAD-fmk
112. Adenovirus E4 open reading frame 4-induced apoptosis involves dysregulation of Src family kinases
113. Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein
114. Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins
115. E4 gene function in adenovirus, adenovirus vector and adeno-associated virus infections
116. Regulated RNA processing and RNA transport during adenovirus infection
117. The adenovirus type 5 E1b 55K and E4 Orf3 proteins associate in infected cells and affect ND10 components
118. ATF-2 contains a phosphorylation-dependent transcriptional activation domain
119. Caspase activation by adenovirus E4orf4 protein is cell line specific and is mediated by the death receptor pathway
120. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination
121. In vitro and in vivo biology of recombinant adenovirus vectors with E1. E1/E2A, or E1/E4 deleted
122. Regulation of adenovirus-mediated transgene expression by the viral E4 gene products: Requirement for E4 ORF3
123. Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein
124. Adenovirus type 5 early region 4 is responsible for E1A-induced p53-independent apoptosis
125. The early region 4 orf4 protein of human adenovirus type 5 induces p53-independent cell death by apoptosis
126. Induction of p53-independent apoptosis by the adenovirus E4orf4 protein requires binding to the Balpha subunit of protein phosphatase 2A
127. The adenovirus E4 17-kilodalton protein complexes with the cellular transcription factor E2F, altering its DNA-binding properties and stimulating E1A-independent accumulation of E2 mRNA
128. Early region 4 modulates adenovirus DNA replication by two genetically separable mechanisms
129. Oncogenic potential of the adenovirus E4orf6 protein
130. Adenovirus E4orf4 protein reduces phosphorylation of c-Fos and E1A proteins while simultaneously reducing the level of AP-1
131. Genetic analysis of the adenovirus E4 6/7 trans activator: Interaction with E2F and induction of a stable DNA-protein complex are critical for activity
132. An adenovirus E4 gene product trans-activates E2 transcription and stimulates stable E2F binding through a direct association with E2F
133. The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function
134. The adenovirus E4orf6 protein contributes to malignant transformation by antagonizing E1A-induced accumulation of the tumor suppressor protein p53
135. Transforming potential of the adenovirus type 5 E4orf3 protein
136. Two distinct activities contribute to the oncogenic potential of the adenovirus type 5 E4orf6 protein
137. 'Hit-and-run' transformation by adenovirus oncogenes
138. Cell transformation by viruses
139. Regulation of early adenovirus transcription: A protein product of early region 2 specifically represses region 4 transcription
140. Regulation of the primary expression of the early adenovirus transcription units
141. Creation and repair of specific DNA double-strand breaks in vivo following infection with adenovirus vectors expressing Saccharomyces cerevisiae HO endonuclease
142. The adenovirus E4-ORF4 splicing enhancer protein interacts with a subset of phosphorylated SR proteins
143. The C-terminal 70 amino acids of the adenovirus E4-ORF6/7 protein are essential and sufficient for E2F complex formation
144. Mutually exclusive interaction of the adenovirus E4-6/7 protein and the retinoblastoma gene product with internal domains of E2F-1 and DP-1
145. The E4-6/7 protein functionally compensates for the loss of E1A expression in adenovirus infection
146. Effect of adenovirus-2 early region 4 products on E1 transformation
147. Toxicological comparison of E2a-deleted and first-generation adenoviral vectors expressing alpha1-antitrypsin after systemic delivery
148. The adenovirus E4-6/7 protein transactivates the E2 promoter by inducing dimerization of a heteromeric E2F complex
149. An arginine-faced amphipathic alpha helix is required for adenovirus type 5 E4orf6 protein function
150. Localization of the adenovirus early region 1B 55-kilodalton protein during lytic infection: Association with nuclear viral inclusions requires the early region 4 34-kilodalton protein
151. Activation of RNA polymerase III transcription of human Alu repetitive elements by adenovirus type 5: Requirement for the E1b 58-kilodalton protein and the products of E4 open reading frames 3 and 6
152. The adenovirus E1B-55K transforming polypeptide modulates transport or cytoplasmic stabilization of viral and host cell mRNAs
153. Adenovirus infection induces rearrangements in the intranuclear distribution of the nuclear body-associated PML protein
154. Role of tyrosine phosphorylation of a cellular protein in adeno-associated virus 2-mediated transgene expression
155. Adeno-associated virus type 2-mediated gene transfer: Correlation of tyrosine phosphorylation of the cellular single-stranded D sequence-binding protein with transgene expression in human cells in vitro and murine tissues in vivo
156. Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells
157. Identification of three functions of the adenovirus e4orf6 protein that mediate p53 degradation by the E4orf6-E1B55K complex
158. Adenovirus late gene expression does not require a rev-like nuclear RNA export pathway
159. Infection of endothelium with E1(-)E4(+), but not E1(-)E4(-), adenovirus gene transfer vectors enhances leukocyte adhesion and migration by modulation of ICAM-1, VCAM-1, CD34, and chemokine expression
160. E1(-)E4(+) adenoviral gene transfer vectors function as a 'pro-life' signal to promote survival of primary human endothelial cells
161. Induction of endogenous genes following infection of human endothelial cells with an E1(-) E4(+) adenovirus gene transfer vector
162. DNA-binding activity of the adenovirus-induced E4F transcription factor is regulated by phosphorylation
163. The adenovirus E4 gene, in addition to the E1A gene, is important for trans-activation of E2 transcription and for E2F activation
164. E4F and ATF, two transcription factors that recognize the same site, can be distinguished both physically and functionally: A role for E4F in E1A trans activation
165. Chromosomal location and tissue expression of the gene encoding the adenovirus E1A-regulated transcription factor E4F in humans and mice
166. Defective synthesis of early region 4 mRNAs during abortive adenovirus infections in monkey cells
167. Inactivation of p53 but not p73 by adenovirus type 5 E1B 55-Kilodalton and E4 34-Kilodalton oncoproteins
168. Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells
169. Viruses and apoptosis
170. Structural analysis of the adenovirus type 5 E1B 55-kilodalton-E4orf6 protein complex
171. Update on adenovirus and its vectors
172. Adenovirus E1B 55-Mr polypeptide facilitates timely cytoplasmic accumulation of adeno-associated virus mRNAs
173. Adenovirus early region 4 is essential for normal stability of late nuclear RNAs
174. p53 is involved in the p120E4F-mediated growth arrest
175. Two independent molecular pathways for recombinant adeno-associated virus genome conversion occur after UV-C and E4orf6 augmentation of transduction
176. Identification and characterization of an immunologically conserved adenovirus early region 11,000 Mr protein and its association with the nuclear matrix
177. Adenovirus early region 1B 58,000-dalton tumor antigen is physically associated with an early region 4 25,000-dalton protein in productively infected cells
178. Induction of the cellular E2F-1 promoter by the adenovirus E4-6/7 protein
179. The PML nuclear bodies: Actors or extras?
180. Analyses of single-amino-acid substitution mutants of adenovirus type 5 E1B-55K protein
181. Adenoviridae: The viruses and their replication
182. Expression of the E4 gene is required for establishment of soft-agar colony-forming rat cell lines transformed by the adenovirus 12 E1 gene
183. Adenovirus type 5 E4 open reading frame 4 protein induces apoptosis in transformed cells
184. Induction of apoptosis by adenovirus E4-open-reading-frame-4 protein is specific to transformed cells and requires an interaction with protein phosphatase 2A
185. Adenovirus E4orf4 protein interacts with both Balpha and B' subunits of protein phosphatase 2A, but E4orf4-induced apoptosis is mediated only by the interaction with Balpha
186. Overexpression of E2F-1 in rat embryo fibroblasts leads to neoplastic transformation
187. Intranuclear location of the adenovirus type 5 E1B 55-kilodalton protein
188. The DNA-dependent protein kinase
189. The complete nucleotide sequence of the DNA of human adenovirus type 12
190. The large E1B protein together with the E4orf6 protein target p53 for active degradation in adenovirus infected cells
191. Distinct regulation of p53 and p73 activity by adenovirus E1A. E1B, and E4orf6 proteins
192. DNA replication of first-generation adenovirus vectors in tumor cells
193. Nuclear dots: Actors on many stages
194. AR1 is an integral part of the adenovirus type 2 E1A-CR3 transactivation domain
195. p53-independent apoptotic and necrotic cell deaths induced by adenovirus infection: Suppression by E1B 19K and Bcl-2 Proteins Cell
196. Adeno-associated virus-based vectors in gene therapy
197. Regulation of apoptosis by viral gene products
198. Adenovirus E1A proteins induce apoptosis by both p53-dependent and p53-independent mechanisms
199. PML nuclear bodies are general targets for inflammation and cell proliferation
200. Early region 1 transforming functions are dispensable for mammary tumorigenesis by human adenovirus type 9
201. Several E4 region functions influence mammary tumorigenesis by human adenovirus type 9
202. Splice junctions in adenovirus 2 early region 4 mRNAs: Multiple splice sites produce 18 to 24 RNAs
203. The adenovirus E4 ORF6 and E1b 55 kDa proteins cooperate in a p53- independent manner to enhance transduction by recombinant adeno- associated virus vectors
204. mRNAs from human adenovirus 2 early region 4
205. Persistent transgene expression in mouse liver following in vivo gene transfer with a delta E1/delta E4 adenovirus vector
206. Identification of two transcription factors that bind to specific elements in the promoter of the adenovirus early-region 4
207. Deletion of the E4 region of the genome produces adenovirus DNA concatemers
208. The nuclear export signal within the E4orf6 protein of adenovirus type 5 supports virus replication and cytoplasmic accumulation of viral mRNA
209. Adenoviral early region 4 is required for efficient viral DNA replication and for late gene expression
210. A carboxy-terminal region required by the adenovirus type 9 E4 ORF1 oncoprotein for transformation mediates direct binding to cellular polypeptides
211. Human adenovirus type 9 E4 open reading frame 1 encodes a cytoplasmic transforming protein capable of increasing the oncogenicity of CREF cells
212. Mutant adenovirus type 9 E4 ORF1 genes define three protein regions required for transformation of CREF cells
213. Human adenovirus early region 4 open reading frame 1 genes encode growth-transforming proteins that may be distantly related to dUTP pyrophosphatase enzymes
214. Serine/threonine protein phosphatases
215. Recombinant, replication-defective adenovirus gene transfer vectors induce cell cycle dysregulation and inappropriate expression of cyclin proteins
216. Phosphorylation within the transactivation domain of adenovirus E1A protein by mitogen-activated protein kinase regulates expression of early region 4
217. Viral and cellular factors that target the promyelocytic leukemia oncogenic domains strongly activate a glucocorticoid-responsive promoter
218. E1B 55-kilodalton oncoproteins of adenovirus types 5 and 12 inactivate and relocalize p53, but not p51 or p73, and cooperate with E4orf6 proteins to destabilize p53
219. Multiple members of the E2F transcription factor family are the products of oncogenes
220. Induction of transformation and p53-dependent apoptosis by adenovirus type 5 E4orf6/7 cDNA
221. Role of adenovirus type 2 early region 4 in the early-to-late switch during productive infection
222. Transforming and oncogenic properties of the adenovirus genome
223. Proto-oncogene PML controls genes devoted to MHC class I antigen presentation
224. A role for PML and the nuclear body in genomic stability