p49/STRAP is a novel protein involved in gene regulation and cell proliferation
Inventors
Wei, Jeanne Y. • Zhang, Xiaomin
Assignees
US Department of Veterans Affairs • BioVentures LLC
Publication Number
US-8232098-B2
Publication Date
2012-07-31
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 provides isolated p49/STRAP protein and isolated nucleic acids encoding the p49/STRAP protein. p49/STRAP is a newly discovered protein expressed in cardiac tissue and other mammalian tissues that binds to serum response factor (SRF) and regulates transcription of SRF-responsive genes in the heart. Importantly, p49/STRAP inhibits tumor cell proliferation, enabling methods of inhibiting cancer cell proliferation by contacting cells with p49/STRAP.
Cardiac disease is a leading cause of death, with increasing incidence during aging. SRF, a key transcription factor in muscle and other tissues, regulates cardiac genes during development and aging and controls cell proliferation, size, and survival. SRF binds to serum response element (SRE) in target gene promoters and recruits cofactors that modulate its function. The bidirectional regulation of SRF target genes suggests that cofactors, including p49/STRAP, may exert positive or negative modulatory effects on SRF-driven gene expression and cell proliferation.
The invention addresses the need for new tools to understand cardiac disease biology and age-related cardiac changes, tools to screen for genetic susceptibility, and materials to reverse or halt cardiac deterioration. In addition, since cancer is a major cause of death, the invention also provides new methods and materials to inhibit cancer cell proliferation and treat cancer.
Claims Coverage
The claims include three independent claims covering isolated nucleic acids encoding p49/STRAP protein adapted for expression in recombinant host cells, and methods of inhibiting cancer cell proliferation and detecting SRF.
Isolated nucleic acid encoding p49/STRAP protein adapted for recombinant expression
An isolated nucleic acid comprising a p49/STRAP gene that encodes a protein at least 90% identical to SEQ ID NO:1 (human) or SEQ ID NO:2 (mouse), wherein the nucleic acid is adapted to express the p49/STRAP protein in a recombinant host cell.
Method of inhibiting cancer cell proliferation using p49/STRAP
A method of inhibiting proliferation of cancer cells by contacting the cancer cells with an effective amount of p49/STRAP protein or by transforming the cancer cells with a recombinant nucleic acid encoding p49/STRAP and expressing it.
Method of detecting SRF using p49/STRAP binding
A method of detecting serum response factor (SRF) in a sample by contacting the sample with labeled p49/STRAP or a SRF-binding peptide thereof and detecting the label, leveraging the tight binding of p49/STRAP to SRF.
The claims collectively cover isolated nucleic acids encoding p49/STRAP proteins with high sequence identity, the use of p49/STRAP to inhibit cancer cell proliferation, and the use of p49/STRAP or derived peptides to detect SRF, highlighting the protein's roles in gene regulation, cancer proliferation inhibition, and molecular detection.
Stated Advantages
p49/STRAP inhibits tumor cell proliferation, causing cell cycle arrest and reducing cancer cell growth.
p49/STRAP can modulate cardiac gene expression during adult aging and disease, providing a target for therapeutic intervention.
The ability of p49/STRAP to bind SRF at a distinct domain allows simultaneous binding with other cofactors, enabling complex regulation of gene transcription.
Nucleic acids encoding p49/STRAP enable screening for genetic diseases related to cardiac and other tissue dysfunctions.
p49/STRAP and related materials provide tools to develop drugs potentially reversing age-related cardiac decline or treating cancer.
Documented Applications
Inhibiting proliferation of cancer cells, including colon cancer cells, by treatment with p49/STRAP protein or expression from recombinant nucleic acid.
Screening for genetic susceptibility and disease in cardiac and other tissues by using nucleic acids encoding p49/STRAP.
Developing drugs targeting p49/STRAP or its gene to reverse or halt age-related declines in cardiac function.
Using p49/STRAP protein or peptide for molecular detection assays of SRF presence and activity.
Studying cardiac gene regulation and age-related changes by analyzing p49/STRAP expression and interactions with SRF and cofactors.
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