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.
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.
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Spain.
Inmaculada
I
Monleón
María
M
Iturralde
María José
MJ
Martínez-Lorenzo
Luis
L
Monteagudo
Pilar
P
Lasierra
Luis
L
Larrad
Andrés
A
Piñeiro
Javier
J
Naval
María Angeles
MA
Alava
Alberto
A
Anel
D000429:Alcohol Oxidoreductases; D015703:Antigens, CD / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019169:Jurkat Cells; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D008563:Membrane Lipids / Q000378:metabolism; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism; D014157:Transcription Factors; D019014:fas Receptor / Q000378:metabolism*
D015703:Antigens, CD; D017252:CD3 Complex; D002352:Carrier Proteins; C119945:Ctbp1 protein, rat; D004268:DNA-Binding Proteins; D051907:Lysosomal Membrane Proteins; D008563:Membrane Lipids; D010750:Phosphoproteins; C402207:SERPINA3 protein, Bos taurus; D015843:Serpins; D014157:Transcription Factors; D019014:fas Receptor; D016718:Arachidonic Acid; D008985:Monensin; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D006867:Hydrolases