Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth

H. G.H. Wang, Y. Rikitake, M. C. Carter, P. Yaciuk, S. E. Abraham, B. Zerler, Elizabeth Moran

Research output: Contribution to journalArticle

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Abstract

Adenovirus early region 1A (E1A) oncogene-encoded sequences essential for transformation- and cell growth-regulating activities are localized at the N terminus and in regions of highly conserved amino acid sequence designated conserved regions 1 and 2. These regions interact to form the binding sites for two classes of cellular proteins: those, such as the retinoblastoma gene product, whose association with the E1A products is specifically dependent on region 2, and another class which so far is known to include only a large cellular DNA-binding protein, p300, whose association with the E1A products is specifically dependent on the N-terminal region. Association between the E1A products and either class of cellular proteins can be disrupted by mutations in conserved region 1. While region 2 has been studied intensively, very little is known so far concerning the nature of the essential residues in the N-terminal region, or about the manner in which conserved region 1 participates in the binding of two distinct sets of cellular proteins. A combination of site-directed point mutagenesis and monoclonal antibody competition experiments reported here suggests that p300 binding is dependent on specific, conserved residues in the N terminus, including positively charged residues at positions 2 and 3 of the E1A proteins, and that p300 and pRB bind to distinct, nonoverlapping subregions within conserved region 1. The availability of precise point mutations disrupting p300 binding supports previous data linking p300 with cell cycle control and enhancer function.

Original languageEnglish (US)
Pages (from-to)476-488
Number of pages13
JournalJournal of virology
Volume67
Issue number1
StatePublished - Jan 1 1993

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Adenoviridae
cell growth
Carrier Proteins
Growth
Proteins
proteins
Retinoblastoma Genes
DNA-binding proteins
oncogenes
DNA-Binding Proteins
point mutation
Site-Directed Mutagenesis
Cell Cycle Checkpoints
Oncogenes
Point Mutation
mutagenesis
binding sites
Amino Acid Sequence
cell cycle
monoclonal antibodies

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Wang, H. G. H., Rikitake, Y., Carter, M. C., Yaciuk, P., Abraham, S. E., Zerler, B., & Moran, E. (1993). Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth. Journal of virology, 67(1), 476-488.
Wang, H. G.H. ; Rikitake, Y. ; Carter, M. C. ; Yaciuk, P. ; Abraham, S. E. ; Zerler, B. ; Moran, Elizabeth. / Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth. In: Journal of virology. 1993 ; Vol. 67, No. 1. pp. 476-488.
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abstract = "Adenovirus early region 1A (E1A) oncogene-encoded sequences essential for transformation- and cell growth-regulating activities are localized at the N terminus and in regions of highly conserved amino acid sequence designated conserved regions 1 and 2. These regions interact to form the binding sites for two classes of cellular proteins: those, such as the retinoblastoma gene product, whose association with the E1A products is specifically dependent on region 2, and another class which so far is known to include only a large cellular DNA-binding protein, p300, whose association with the E1A products is specifically dependent on the N-terminal region. Association between the E1A products and either class of cellular proteins can be disrupted by mutations in conserved region 1. While region 2 has been studied intensively, very little is known so far concerning the nature of the essential residues in the N-terminal region, or about the manner in which conserved region 1 participates in the binding of two distinct sets of cellular proteins. A combination of site-directed point mutagenesis and monoclonal antibody competition experiments reported here suggests that p300 binding is dependent on specific, conserved residues in the N terminus, including positively charged residues at positions 2 and 3 of the E1A proteins, and that p300 and pRB bind to distinct, nonoverlapping subregions within conserved region 1. The availability of precise point mutations disrupting p300 binding supports previous data linking p300 with cell cycle control and enhancer function.",
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Wang, HGH, Rikitake, Y, Carter, MC, Yaciuk, P, Abraham, SE, Zerler, B & Moran, E 1993, 'Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth', Journal of virology, vol. 67, no. 1, pp. 476-488.

Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth. / Wang, H. G.H.; Rikitake, Y.; Carter, M. C.; Yaciuk, P.; Abraham, S. E.; Zerler, B.; Moran, Elizabeth.

In: Journal of virology, Vol. 67, No. 1, 01.01.1993, p. 476-488.

Research output: Contribution to journalArticle

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AU - Wang, H. G.H.

AU - Rikitake, Y.

AU - Carter, M. C.

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AU - Moran, Elizabeth

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N2 - Adenovirus early region 1A (E1A) oncogene-encoded sequences essential for transformation- and cell growth-regulating activities are localized at the N terminus and in regions of highly conserved amino acid sequence designated conserved regions 1 and 2. These regions interact to form the binding sites for two classes of cellular proteins: those, such as the retinoblastoma gene product, whose association with the E1A products is specifically dependent on region 2, and another class which so far is known to include only a large cellular DNA-binding protein, p300, whose association with the E1A products is specifically dependent on the N-terminal region. Association between the E1A products and either class of cellular proteins can be disrupted by mutations in conserved region 1. While region 2 has been studied intensively, very little is known so far concerning the nature of the essential residues in the N-terminal region, or about the manner in which conserved region 1 participates in the binding of two distinct sets of cellular proteins. A combination of site-directed point mutagenesis and monoclonal antibody competition experiments reported here suggests that p300 binding is dependent on specific, conserved residues in the N terminus, including positively charged residues at positions 2 and 3 of the E1A proteins, and that p300 and pRB bind to distinct, nonoverlapping subregions within conserved region 1. The availability of precise point mutations disrupting p300 binding supports previous data linking p300 with cell cycle control and enhancer function.

AB - Adenovirus early region 1A (E1A) oncogene-encoded sequences essential for transformation- and cell growth-regulating activities are localized at the N terminus and in regions of highly conserved amino acid sequence designated conserved regions 1 and 2. These regions interact to form the binding sites for two classes of cellular proteins: those, such as the retinoblastoma gene product, whose association with the E1A products is specifically dependent on region 2, and another class which so far is known to include only a large cellular DNA-binding protein, p300, whose association with the E1A products is specifically dependent on the N-terminal region. Association between the E1A products and either class of cellular proteins can be disrupted by mutations in conserved region 1. While region 2 has been studied intensively, very little is known so far concerning the nature of the essential residues in the N-terminal region, or about the manner in which conserved region 1 participates in the binding of two distinct sets of cellular proteins. A combination of site-directed point mutagenesis and monoclonal antibody competition experiments reported here suggests that p300 binding is dependent on specific, conserved residues in the N terminus, including positively charged residues at positions 2 and 3 of the E1A proteins, and that p300 and pRB bind to distinct, nonoverlapping subregions within conserved region 1. The availability of precise point mutations disrupting p300 binding supports previous data linking p300 with cell cycle control and enhancer function.

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