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© The Rockefeller University Press, 0021-9525/1998//153 $5.00
The Journal of Cell Biology, Volume 140, Number 1, , 1998 153-158


Article

A Role for Caspases in Lens Fiber Differentiation



Yasuki Ishizaki*, Michael D. Jacobson{ddagger}, and Martin C. Raff{ddagger}

* Department of Hygiene, Kobe University School of Medicine, Chuo-ku, Kobe 650, Japan; and {ddagger} Medical Research Council Laboratory for Molecular Cell Biology and Biology Department, University College London, London WC1E 6BT, United Kingdom

There is increasing evidence that programmed cell death (PCD) depends on a novel family of intracellular cysteine proteases, called caspases, that includes the Ced-3 protease in the nematode Caenorhabditis elegans and the interleukin-1β–converting enzyme (ICE)-like proteases in mammals. Some developing cells, including lens epithelial cells, erythroblasts, and keratinocytes, lose their nucleus and other organelles when they terminally differentiate, but it is not known whether the enzymatic machinery of PCD is involved in any of these normal differentiation events. We show here that at least one CPP32 (caspase-3)-like member of the caspase family becomes activated when rodent lens epithelial cells terminally differentiate into anucleate lens fibers in vivo, and that a peptide inhibitor of these proteases blocks the denucleation process in an in vitro model of lens fiber differentiation. These findings suggest that at least part of the machinery of PCD is involved in lens fiber differentiation.


Abbreviations used in this paper: bFGF, basic fibroblast growth factor; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; P, postnatal day; PCD, programmed cell death; PARP, poly(ADP-ribose) polymerase; STS, staurosporine; TUNEL, terminal deoxynucleotidyl transferase [Tdt]-mediated dUTP-biotin nick-end labeling.

Address all correspondence to Martin C. Raff, Medical Research Council Laboratory for Molecular Cell Biology and Biology Department, University College London, London WC1E 6BT, United Kingdom. Tel.: (44) 171.380.7016. Fax: (44) 171.380.7805. E-mail: m.raff{at}ucl.ac.uk



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