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 structures

Inmaculada Monleón; María Iturralde; María José Martínez-Lorenzo; Luis Monteagudo; Pilar Lasierra; Luis Larrad; Andrés Piñeiro; Javier Naval; María Angeles Alava; Alberto Anel

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 structures

Cell Growth Differ. 2002 Jul;13(7):315-24.

Authors

Inmaculada Monleón¹, María Iturralde, María José Martínez-Lorenzo, Luis Monteagudo, Pilar Lasierra, Luis Larrad, Andrés Piñeiro, Javier Naval, María Angeles Alava, Alberto Anel

Affiliation

¹ Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Spain.

PMID: 12133900

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alcohol Oxidoreductases
Antigens, CD / metabolism
Arachidonic Acid / metabolism
CD3 Complex / metabolism
Carrier Proteins / metabolism*
Cell Division / physiology*
Cell Membrane / metabolism*
Cell Membrane / ultrastructure
Cell Transformation, Neoplastic / metabolism*
Cytoplasm / metabolism
Cytoplasm / ultrastructure
DNA-Binding Proteins / metabolism*
Gene Expression Regulation, Leukemic / physiology
Humans
Hydrolases / antagonists & inhibitors
Hydrolases / metabolism
Jurkat Cells
Leukemia / genetics
Leukemia / metabolism
Leukemia / physiopathology
Lysosomal Membrane Proteins
Lysosomes / metabolism*
Lysosomes / ultrastructure
Membrane Lipids / metabolism
Microscopy, Electron
Monensin / pharmacology
Phosphoproteins / metabolism*
Serpins / metabolism
Transcription Factors*
fas Receptor / metabolism*

Substances

Antigens, CD
CD3 Complex
Carrier Proteins
Ctbp1 protein, rat
DNA-Binding Proteins
Lysosomal Membrane Proteins
Membrane Lipids
Phosphoproteins
SERPINA3 protein, Bos taurus
Serpins
Transcription Factors
fas Receptor
Arachidonic Acid
Monensin
Alcohol Oxidoreductases
C-terminal binding protein
Hydrolases