Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 4 (9), 874-81

The Threshold Pattern of Calcineurin-Dependent Gene Expression Is Altered by Loss of the Endogenous Inhibitor Calcipressin

Affiliations

The Threshold Pattern of Calcineurin-Dependent Gene Expression Is Altered by Loss of the Endogenous Inhibitor Calcipressin

Sandra Ryeom et al. Nat Immunol.

Abstract

Calcineurin links calcium signaling to transcriptional responses in the immune, nervous and cardiovascular systems. To determine the function of the calcipressins, a family of putative calcineurin inhibitors, we assessed the calcineurin-dependent process of T cell activation in mice engineered to lack the gene encoding calcipressin 1 (Csp1). Csp1 regulated calcineurin in vivo, and genes triggered in an immune response had unique transactivation thresholds for T cell receptor stimulation. In the absence of Csp1, the apparent transactivation thresholds for all these genes were shifted because of enhanced calcineurin activity. This unbridled calcineurin activity drove Fas ligand expression, which normally requires high T cell receptor stimulation and results in the premature death of T helper type 1 cells. Thus, calcipressins modulate the pattern of calcineurin-dependent transcription, and may influence calcineurin activity beyond calcium to integrate a broad array of signals into the cellular response.

Comment in

Similar articles

See all similar articles

Cited by 42 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback