Human regulatory molecules

Abstract

The invention provides human regulatory molecules and the polynucleotides which identify and encode them. The invention also provides expression vectors, host cells, agonists, antibodies and antagonists. The invention further provides methods for diagnosing and treating disorders associated with expression of human regulatory molecules.

Description

[0001] This application is a divisional of U.S. Pat. No. 09 / 518,865 filed 3 Mar. 2000, which was a divisional of U.S. Pat. No 6,132,973, issued 17 Oct. 2000, which was a divisional of U.S. Pat. No. 5,932,442, issued 3 Aug. 1999.[0002] This invention relates to nucleic acid and amino acid sequences of human regulatory molecules which are implicated in disease and to the use of these sequences in the diagnosis and treatment of diseases associated with cell proliferation.[0003] Cells grow and differentiate, carry out their structural or metabolic roles, participate in organismal development, and respond to their environment by altering their gene expression. Cellular functions are controlled by the timing and amount of expression attributable to thousands of individual genes. The regulation of expression is metabolically vital in that it conserves energy and prevents the synthesis and accumulation of intermediates such as RNA and incomplete or inactive proteins when the gene product is...

AI Technical Summary

Benefits of technology

[0161] Although polynucleotides which encode HRM and its variants are preferably capable of hybridizing to the polynucleotide of the naturally occurring HRM under selected conditions of stringency, it may be advantageous to produce polynucleotides encoding HRM or its derivatives possessing a different codon usage. Codons may be selected to increase the rate at which expression of the peptide occurs in a particular prokaryotic or eukaryotic host in accordance with the frequency with which particular codons are utilized by the host. Other reasons for altering the polynucleotide encoding HRM and its derivatives without altering the encoded amino acid sequences include the production of RNA transcripts having more desirable properties, such as a greater half-life, than transcripts produced from the naturally occurring sequence.

[0269] Fluorescent in situ hybridization (FISH as described in Verma et al. (1988) Human Chromosomes: A Manual of Basic Techniques, Pergamon Press, New York N.Y.) may be correlated with other physical chromosome mapping techniques and genetic map data. Examples of genetic map data can be found in various scientific journals or at Online Mendelian Inheritance in Man (OMIM). Correlation between the location of the gene encoding HRM on a physical chromosomal map and a specific disease, or predisposition to a specific disease, may help delimit the region of DNA associated with that genetic disease. The polynucleotides of the invention may be used to detect differences in gene sequences between normal, carrier, or affected individuals.

Problems solved by technology

Although binding of DNA to a regulatory protein is very specific, there is no way to predict the exact DNA sequence to which a particular regulatory protein will bind or the primary structure of a regulatory protein for a specific DNA sequence.

Alternatively, gene fusion may produce chimeric loci with switched domains, such that the level of activation is no longer correct for the gene specificity of that factor.

However, when hyper-responsivity or another imbalance occurs for any reason, disregulation of gene expression may cause considerable tissue or organ damage.

In addition, the accumulation of somatic mutations and the increasing inability to regulate cellular responses is seen in the prevalence of osteoarthritis and onset of other aging disorders.