Apoptosis-associated proteolysis of vimentin in human prostate epithelial tumor cells.
Vimentin intermediate filaments (IF) are responsible for regulation of cell attachment and subcellular organization. Using an in vitro model system of human prostate epithelial cells (267B1-XR), we demonstrate that a series of vimentin proteolytic fragments represent some of the differentially expressed proteins in 2D-gel profiles of the apoptotic cells undergoing ionizing radiation-induced cell death. A caspase-sensitive motif search suggests that the type III IF protein (vimentin) is subject to proteolysis to promote the execution phase of apoptosis, in a manner similar to the well-established type V (lamins) and type I (keratins 18, 19) IF proteins. Furthermore, vimentin and a few of its derived polypeptides, reported to be specific to the apoptotic process, correspond to ubiquinated proteins, thus pointing to the complex interrelationships of protein ubiquination in solubilizing the IF network during apoptosis.
Department of Radiation Medicine, Division of Radiation Research, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA. prasads@gunet.georgetown.edu
S C
SC
Prasad
P J
PJ
Thraves
M R
MR
Kuettel
G Y
GY
Srinivasarao
A
A
Dritschilo
V A
VA
Soldatenkov
D017209:Apoptosis; D001665:Binding Sites; D015153:Blotting, Western; D020170:Caspase 1; D053178:Caspase 6; D020169:Caspases; D002448:Cell Adhesion; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D010450:Endopeptidases / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000378:metabolism; D034882:Lamins; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism*
D034882:Lamins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D014746:Vimentin; D007633:Keratins; D011065:Poly(ADP-ribose) Polymerases; D010450:Endopeptidases; C505514:CASP6 protein, human; D053178:Caspase 6; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1