Cell Growth & Differentiation Vol. 13, 315-324, July 2002
© 2002 American Association for Cancer Research
Lack of Fas/CD95 Surface Expression in Highly Proliferative Leukemic Cell Lines Correlates with Loss of CtBP/BARS and Redirection of the Protein toward Giant Lysosomal Structures1
María José Martínez-Lorenzo,
María Angeles Alava and
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias [I. M., M. I., A. P., J. N., M. A. A., A. A.]; Servicio de Inmunología, Hospital Clínico Universitario [M. J. M-L., L. L., P. L.]; and Departamento de Anatomía, Embriología y Genética, Facultad de Veterinaria [L. M.], Universidad de Zaragoza, Zaragoza E-50009, Spain
Fas/CD95 is a type-I membrane glycoprotein, which inducesapoptotic cell death when ligated by its physiological ligand. We generated previously hyperproliferative sublines derived from the human T-cell leukemia Jurkat, Jurkat-ws and Jurkat-hp, which lost Fas/CD95 surface expression. We have now observed that the total amount of Fas protein is similar in the sublines and in the parental cells, indicating that in the sublines Fas remains in an intracellular compartment. We have found that the protein is directed toward lysosomes in the sublines, where it is degraded. This defect in the secretory pathway correlates with loss of polyunsaturated fatty acids from cellular lipids, and with the lack of expression of endophilin-I and CtBP/BARS, enzymes that regulate vesicle fission by catalyzing the acylation of arachidonate into lysophosphatidic acid. In addition, great multillamer bodies, which contained acid phosphatase activity, absent in the parental Jurkat cells, were observed by transmission electron microscopy in the sublines.
Copyright © 2002 by the American Association of Cancer Research.