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., Rikitake, Y., Carter, M. C., Yaciuk, P., Abraham, S. E., Zerler, B., Moran, E. (January 1993) Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth. J Virol, 67 (1). pp. 476-88. ISSN 0022-538X (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/8416379

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.

Item Type: Paper
Uncontrolled Keywords: Adenovirus E1A Proteins/ genetics/ metabolism/pharmacology Amino Acid Sequence Animals Cell Differentiation Cell Division/drug effects Cell Line Cell Transformation, Viral/drug effects/ genetics DNA Mutational Analysis DNA-Binding Proteins/ metabolism Enhancer Elements (Genetics) Humans Models, Genetic Molecular Sequence Data Protein Conformation Research Support, U.S. Gov't, P.H.S. Retinoblastoma Protein/metabolism Sequence Homology, Amino Acid Structure-Activity Relationship Tyrosine
Subjects: organism description > virus > adenovirus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > DNA binding protein
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: January 1993
Date Deposited: 18 Apr 2016 18:48
Last Modified: 18 Apr 2016 18:48
PMCID: PMC237385
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32528

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