Editors' ChoiceCell Cycle

Loss of FKBP12 Applies the Brakes

Science's STKE  06 Mar 2001:
Vol. 2001, Issue 72, pp. tw4
DOI: 10.1126/stke.2001.72.tw4

FKBP12 is a 12-kD protein originally identified as the physiologic target for the immunosuppressive drug FK506. FKBP12 is widely expressed and attenuates the activity of inositol trisphosphate receptors, ryanodine receptors, and transforming growth factor β receptors (TGFβRs). FKBP12 is essential, and knockout mice die as embryos; however, Aghdasi et al. were able to study embryonic fibroblasts from FKBP12-/- mice in culture. The FKBP12-/- fibroblasts divided more slowly than did wild-type fibroblasts and exhibited cell-cycle arrest in G1, which could be overcome in cells expressing a dominant negative TGFβR mutant. Analysis of the potential signaling pathways activated by TGFβR (SMAD pathway or the ERK or p38 mitogen-activated kinase pathways) indicated that the hyperactive TGFβR pathway responsible for the cell-cycle arrest was the p38 pathway leading to overexpression of the cyclin-dependent kinase inhibitor p21.

B. Aghdasi, K. Ye, A. Resnick, A. Huang, H. C. Ha, X. Guo, T. M. Dawson, V. L. Dawson, S. H. Snyder, FKBP12, the 12-kDa FK506-binding protein, is a physiologic regulator of the cell cycle. Proc. Natl. Acad. Sci. U.S.A. 98, 2425-2430 (2001). [Abstract] [Full Text]

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