Figure 12-19. The control of nuclear import during T-cell activation.

Figure 12-19The control of nuclear import during T-cell activation

The nuclear factor of activated T cells (NF-AT) is a gene regulatory protein that, in the resting T cell, is found in the cytosol in a phosphorylated state. When T cells are activated, the intracellular Ca2+ concentration increases. In high Ca2+, the protein phosphatase, calcineurin, binds to NF-AT. Binding of calcineurin dephosphorylates NF-AT, exposing one or more nuclear import signals, and it may also block a nuclear export signal. The complex of NF-AT bound to calcineurin is then imported into the nucleus, where NF-AT activates the transcription of numerous cytokine and cell-surface protein genes that are required for a proper immune response. During the shut-off of the response, decreased Ca2+ levels lead to the release of calcineurin. Rephosphorylation of NF-AT inactivates the nuclear import signal, and it re-exposes the nuclear export signal of NF-AT causing NF-AT to relocate to the cytosol. Some of the most potent immunosuppressive drugs, such as cyclosporin A and FK506, inhibit the ability of calcineurin to dephosphorylate NF-AT; these drugs thereby block the nuclear accumulation of NF-AT.

From: The Transport of Molecules between the Nucleus and the Cytosol

Cover of Molecular Biology of the Cell
Molecular Biology of the Cell. 4th edition.
Alberts B, Johnson A, Lewis J, et al.
New York: Garland Science; 2002.
Copyright © 2002, Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter; Copyright © 1983, 1989, 1994, Bruce Alberts, Dennis Bray, Julian Lewis, Martin Raff, Keith Roberts, and James D. Watson .

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