Degradation of focal adhesion proteins during nocodazole-induced apoptosis in rat-1 cells.
Nocodazole, a microtubule-disrupting agent, induced apoptosis in Rat-1 cells, as indicated by changes in cell morphology, DNA fragmentation, and eventual cell death. During nocodazole-induced apoptosis, normally flat cells became rounded in shape and detached from the extracellular matrix. These morphological changes appeared to be closely associated with degradation of focal adhesion proteins, including p130cas, p125(FAK) and paxillin. p130cas was also degraded in cells treated with staurosporine or etoposide, suggesting that degradation of focal adhesion proteins is a characteristic feature of apoptosis. Nocodazole-induced apoptosis was antagonized by Bcl-2: degradation of focal adhesion proteins was suppressed and cell viability was enhanced in bcl-2 over-expressing cells, even in the presence of nocodazole. Further study of the molecular mechanism of Bcl-2 activation should provide an understanding of the apoptosis induced by disruption of the microtubule network.
Kook
S
S
Department of Life Science and Energy & Environmental Research Center, Kwangju Institute of Science & Technology, Kwangju 500-712, Korea.
Shim
S R
SR
Kim
J I
JI
Ahnn
J H
JH
Jung
Y K
YK
Paik
S G
SG
Song
W K
WK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008870:Microtubules / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D050717:Retinoblastoma-Like Protein p130; D019311:Staurosporine / Q000494:pharmacology
D000970:Antineoplastic Agents; C493843:Bcar1 protein, rat; D015815:Cell Adhesion Molecules; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D051419:Paxillin; D010750:Phosphoproteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C496063:Pxn protein, rat; D050717:Retinoblastoma-Like Protein p130; D005047:Etoposide; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D019311:Staurosporine; D015739:Nocodazole