FAS-associated factor 1 interacts with protein kinase CK2 in vivo upon apoptosis induction.
We show here that in several different cell lines protein kinase CK2 and Fas-associated factor 1 (FAF1) exist together in a complex which is stable to high monovalent salt concentration. The CK2/FAF1 complex formation is significantly increased after induction of apoptosis with various DNA damaging agents. Interestingly this effect is only seen in cell lines with an embryonic origin and not when cells have entered a differentiated state. It is further shown that the CK2 specific phosphorylation sites in the FAF1 molecule, i.e. serines 289 and 291 influence this complex formation. Mutation of the CK2 phosphorylation sites in the FAF1 molecule to alanine leads to a 1.5 to 2.0-fold higher association between CK2 and FAF1. Since the CK2 activity did not increase concomitantly with the complex formation we conclude that the FAF1 becomes to the CK2 enzyme so that a normal enzyme catalysis does not take place anymore. Subcellular localization experiments involving CK2 subunits and FAF1 show a co-localization of both CK2 subunits and FAF1 in the peri-nuclear cytoplasm. The majority of CK2 subunits is found in the nucleus. FAF1 is also found in the nucleoli. The results obtained further support the view that protein kinase CK2 plays an important role in certain steps of apoptosis.
Guerra
B
B
University of Southern Denmark, Odense University, Institute for Biochemistry and Molecular Biology, DK-5230 Odense, Denmark.
Boldyreff
B
B
Issinger
O G
OG
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D047390:Casein Kinase II; D002454:Cell Differentiation; D002945:Cisplatin / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary; D004591:Electrophoresis, Polyacrylamide Gel; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; C490780:FAF1 protein, human; C097186:Faf1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin