Biotech Articles
Publish Your Research Online
Get Recognition - International Audience

Request for an Author Account   |   Login   |   Submit Article

Proteasomes and Their Biological Significance

BY: Sandhya Anand | Category: Biotech-Research | Submitted: 2011-06-14 21:37:44
       No Photo
Article Summary: "The article briefly summarizes the importance of proteasomes in drug designing, biological significance and exploratory studies on evolution..."

Share with Facebook Share with Linkedin Share with Twitter Share with Pinterest Email this article

Proteasomes are instrumental in degradation of damaged or non functional proteins and a variety of other regulatory functions. They comprise of various enzymes which breakdown the proteins into its constituent amino acids.

Because of its multifunctional role and multi subunit nature, the proteasomes are of immense research potential. They are found to be instrumental in viral infections including HIV and hence drug designing approaches using proteasomes are promising.

HIV and proteasomes

HIV virus is one of the classical viruses which employ proteasomes for their infection. The virus has three protein complexes responsible for producing the inner virion core (Gag), the viral enzymes (Pol), and the external glycoprotein envelope (Env).

HIV virus enters the host cell and the genome gets translated. The newly formed Gag protein gets cleaved by proteasomes into matris, capsid and nucleocapsid along with p6 gag proteins. Proteasomes thus function to produce the infectious viral particles.

Selective degradation by proteasomes is often mediated through covalent binding of ubiqutin to the protein and this is employed by HIV. The virus protein Vpu labels the CD4 molecules with ubiquitin making them vulnerable to degradation by proteasomes. CD4 molecules are involved in identification of virally infected cells by T cells and prevent their destruction.

Moreover, the proteasomes are found to play both proteolytic and non proteolytic types of regulation of HIV-1 promoter. The transcription factor, Tat was found to dissociate the proteasomes into its subunits through a mediator proteasome associated protein, PAAF-1. This in turn inhibited the proteolytic activity. Tat also interferes with Class-I presentation of some epitopes. Drugs such as ritonavir block the presentation of viral antigens to Cytotoxic T lymphocytes.

Proteasome inhibitors

The Proteasome association in gene regulation and selective protein degradation had led to the development of proteasome inhibitors as drugs.

Proteasome subunits have different catalytic functions. The inhibitors target these activities which are similar to trypsin, chymotrypsin and the hydrolysis of peptidyl glutamyl peptide bonds. Some of the inhibitors are naturally occurring while others are designed using various approaches of drug designing.

TMCs, Hsp 90, P131 etc are naturally occurring proteasomal inhibitors. Binding site of TMCs is adjacent to the Threonine active site of the enzyme. Hsp 90 inhibits the chymotrypsin like activity and peptidyl glutmyl peptide hydrolysis activity of the 20S subunit.

They are also instrumental in regulation of cell cycle and induction of apoptosis. Proteasomes are therefore potential targets for drug designing approaches for cancer.

They are being recognized as potential drug targets in tuberculosis due to the similarity of the mycobacterial proteasomes with that of eukaryotes. M. Tuberculosis is the only bacterial pathogen known to possess proteasomes.

The use of proteasome inhibitors as anti infectives have so far not been materialized since it is difficult to avoid the inherent risk associated with blocking the natural proteasomes which are important for maintaining cellular activities such as apoptosis. Proteasomal non functioning is also present in neurodegenerative diseases such as Parkinson's, Huntngton's disease etc. This is thought to cause an increase in the protein turn over which can result in death of nervous tissue.

Proteasomes and evolution

These structures are present in primitive organisms such as archebacteria. Euacteria have complex protein degrading machinery with 14 different proteins of 7 alpha and 7 beta chains. However the archebacterial proteasomes have only two proteins with 14 copies of each.

The sequences are comparatively preserved across the species and therefore phylogenetic analyses reveal information on evolutionary history. The subunits alpha and beta are thought to origin as a result of single gene duplication event which must have occurred prior to the divergence of archaebacteria and eukaryotes. The conserved sequence within a single structure is considered as a proof for this view.

The core 20S particle is similar with four ring structures in both archaebacteria and eukaryotic cells. However 20S subunit is made of two peptide chains alone in arachaebacteria. There is a single ATPase called PAN which serves the function in arachaebacteria while in eukaryotes this is replaced by six ATPases.

Study of proteasomes has become more relevant to exploration of evolutionary history with the identification of more primitive organisms. Malfunction of Ubiquitin-proteasome system is found to be associated with many diseases. The involvement of proteasomes in metabolic regulation is also being evident from research studies. This makes them ideal targets for drug designing along with development of methods to reduce the toxicity attributes.

About Author / Additional Info:

Search this site & forums
Share this article with friends:

Share with Facebook Share with Linkedin Share with Twitter Share with Pinterest Email this article

More Social Bookmarks (Digg etc..)

Comments on this article: (0 comments so far)

Comment By Comment

Leave a Comment   |   Article Views: 31405

Additional Articles:

•   Somatic Cell Fusion- A Biotechnology Technique

•   Biological Control of Insect Pests

•   Coir Pith as Organic Soil Less Growing Medium

•   The Latest News on Human Gene Therapies

Latest Articles in "Biotech-Research" category:
•   Human Longevity: A Revolution in Biotechnology and Nanotechnology.

•   Nanoparticles as Delivery Device For Gene Therapy

•   Biotechnology as a Tool in Medicine: Focus on Artemisinin

•   Tissue Cells and Skin Cells Reprogrammed Into Embryonic Stem Cells:-

•   Polymerase Chain Reaction (or PCR) - Technique For Amplifying DNA

•   Treatment of Heart Disease With Stem Cells

•   Biological Activities and Bioassays

•   DNA Sequencing: Maxam Gilbert Method

•   PCR Aspects and its Future | PCR versus Cloning

•   Plasmid as Vectors For Plant Transformation

•   Gene Isolation and Characterisation

•   Apoptosis and Cancer: A Review

•   Extraction of Nucleic Acids (DNA and RNA) From Plant Tissues

•   Stem Cells From Bone Marrow and Vein Leftovers Can Heal Damaged Hearts

•   Gene Transfer Techniques: Biolistics, Bacterial and Viral Transformation

•   Breast Cancer: Cactus For Womens Life

•   Mtt Assay: Assess The Viability Of Cell In Culture

•   Medicinal Plants: Source Of Medicine

•   Biotechnology Impact on Alzheimer's Disease

Important Disclaimer: All articles on this website are for general information only and is not a professional or experts advice. We do not own any responsibility for correctness or authenticity of the information presented in this article, or any loss or injury resulting from it. We do not endorse these articles, we are neither affiliated with the authors of these articles nor responsible for their content. Please see our disclaimer section for complete terms.
Page copy protected against web site content infringement by Copyscape
Copyright © 2010 - Do not copy articles from this website.

Agriculture Bioinformatics Applications Biotech Products Biotech Research
Biology Careers College/Edu DNA Environmental Biotech
Genetics Healthcare Industry News Issues Nanotechnology
Others Stem Cells Press Release Toxicology  

  |   Disclaimer/Privacy/TOS   |   Submission Guidelines   |   Contact Us