The interaction between the catalytic A subunit of calcineurin and its autoinhibitory domain, in the yeast two-hybrid system, is disrupted by cyclosporin A and FK506

FEBS Letters
B ChaudhuriP Fürst

Abstract

The Ca(2+)-calmodulin dependent protein phosphatase, calcineurin, is thought to mediate the action of the two immunosuppressants, cyclosporin A (CsA) and FK506. Calcineurin from all species consists of a catalytic A subunit and a regulatory peptide B, which plays an essential role in catalysis. The enzymatic function is probably also regulated by an autoinhibitory domain (AID) present in the catalytic subunit. We have used the yeast two-hybrid system to show that the putative AID of the yeast catalytic subunit Cna1 binds only to truncated Cna1, devoid of AID. Although deletion of the genes encoding the yeast catalytic subunits of calcineurin (CNA1 and CNA2) maintain the interaction, absence of the regulatory subunit Cnb1 prevents binding. Interestingly, both CsA and FK506 disrupt this interaction, whereas binding of Cna1 to calmodulin remains unaffected. This indicates that a simple cellular system, developed in yeast, could provide further insight into an understanding of calcineurin inhibition.

References

Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M S CyertJ Thorner
Oct 31, 1991·Biochemical and Biophysical Research Communications·T KunoC Tanaka
Oct 13, 1988·Nature·G Hardie
Jan 1, 1986·Cold Spring Harbor Symposia on Quantitative Biology·K MullisH Erlich
Mar 25, 1983·Nucleic Acids Research·R Taussig, M Carlson
Jan 1, 1983·Methods in Enzymology·R J Rothstein
Sep 1, 1993·Trends in Biochemical Sciences·J Kunz, M N Hall
Jan 1, 1994·Annual Review of Biochemistry·G R Crabtree, N A Clipstone

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.