GRAIL: a unique mediator of CD4 T-lymphocyte unresponsiveness


C. G. Fathman, Department of Medicine, Division of Rheumatology and Immunology, Stanford University, 269 Campus Drive West, Stanford, CA 94305, USA
Fax: +1 650 725 1958
Tel: +1 650 723 7887


GRAIL (gene related to anergy in lymphocytes, also known as RNF128), an ubiquitin–protein ligase (E3), utilizes a unique single transmembrane protein with a split-function motif, and is an important gatekeeper of T-cell unresponsiveness. Although it may play a role in other CD4 T-cell functions including activation, survival and differentiation, GRAIL is most well characterized as a negative regulator of T-cell receptor responsiveness and cytokine production. Here, we review the recent literature on this remarkable E3 in the regulation of human and mouse CD4 T-cell unresponsiveness.