Nucleic acid encoding a p49/STRAP protein that binds to serum response factor (SRF) and regulates transcription of SRF-responsive genes in the heart; antitumor and anticarcinogenic agents
Inventors
Wei, Jeanne Y. • Zhang, Xiaomin
Assignees
US Department of Veterans Affairs • University of Arkansas System • BioVentures LLC
Publication Number
US-7498411-B2
Publication Date
2009-03-03
Expiration Date
2025-09-13
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Abstract
The invention provides isolated p49/STRAP protein, and isolated nucleic acids encoding a p49/STRAP protein. The inventors have discovered a new protein, named p49/STRAP that is expressed in cardiac tissue and other tissues in mammals. The p49/STRAP protein binds to serum response factor (SRF) and regulates transcription of SRF-responsive genes in the heart. p49/STRAP is also discovered to inhibit tumor cell proliferation, and thus the invention provides a method of inhibiting cancer cell proliferation by contacting the cells with p49/STRAP.
Core Innovation
The invention is based on the discovery of a novel protein, p49/STRAP, present in humans and mice. This protein binds to the serum response factor (SRF), a transcription factor that regulates cardiac genes during development and aging. The invention provides isolated p49/STRAP protein and isolated nucleic acids encoding the p49/STRAP protein, with specific sequences represented as SEQ ID NO:1 (human protein), SEQ ID NO:2 (mouse protein), SEQ ID NO:3 (human cDNA), and SEQ ID NO:4 (mouse cDNA).
The p49/STRAP protein is unique in that it binds to the COOH-terminal portion of SRF and can coexist on SRF with other cofactors that bind to the NH2-terminal portion. It is highly expressed in cardiac tissue and also found in other tissues such as liver, kidney, and skeletal muscle. The p49/STRAP protein modulates the transcription of multiple cardiac genes, sometimes enhancing and sometimes repressing gene expression in conjunction with SRF.
A significant additional finding is that p49/STRAP inhibits proliferation of tumor cells. The invention describes methods of inhibiting cancer cell proliferation by contacting cells with p49/STRAP protein or by expressing p49/STRAP within the cells. Production of antibodies to p49/STRAP, recombinant cells harboring altered p49/STRAP genes, and methods of detecting SRF using labeled p49/STRAP are also covered within the invention, providing tools for both research and possible therapeutic use.
Claims Coverage
There are two independent claims in this patent, each covering a related but distinct inventive feature regarding p49/STRAP proteins.
Isolated peptide or protein comprising SEQ ID NO:1
This inventive feature is directed toward an isolated peptide or protein that has the exact sequence of SEQ ID NO:1. The sequence SEQ ID NO:1 corresponds to the human p49/STRAP protein, which binds to SRF and modulates SRF-responsive gene transcription.
Isolated p49/STRAP protein that is a human p49/STRAP protein
This feature claims the isolated p49/STRAP protein as identified and described in the invention, specifically specifying that it is a human p49/STRAP protein. The protein is characterized by its ability to bind SRF and influence cardiac gene regulation.
The claims provide coverage for the isolated human p49/STRAP protein, both as a specific amino acid sequence (SEQ ID NO:1) and more generally as the isolated human p49/STRAP protein with the described properties.
Stated Advantages
The invention provides materials useful to screen for genetic susceptibility to heart conditions and to understand heart biology.
It offers materials that may be useful to reverse or halt age-related changes in the heart or cardiac disease.
It provides new tools and materials to inhibit cancer cell proliferation and to treat cancer.
Antibodies and recombinant cells are offered as research tools to study p49/STRAP biology and gene regulation.
Documented Applications
Screening for genetic diseases related to cardiac function using nucleic acids encoding p49/STRAP.
Potential therapeutic intervention for age-related decline in cardiac function by modulating p49/STRAP expression or activity.
Inhibition of tumor cell proliferation, including colon cancer and other specified cancer types, by contacting cells with p49/STRAP protein or expressing p49/STRAP in the cells.
Assays to measure the activity of SRF and its cofactors using p49/STRAP.
Production and use of antibodies that specifically recognize p49/STRAP for biological studies and potential clinical applications.
Use of recombinant cells with insertions or deletions in the p49/STRAP gene to study gene function and explore clinical utility.
Detection of SRF in samples using labeled p49/STRAP or p49/STRAP-derived peptides.
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