Promoting apoptosis: a novel activity associated with the cyclin-dependent kinase inhibitor p27.
p27Kip1, a cyclin-dependent kinase inhibitor, is recognized as a negative regulator of the cell cycle. In this paper, we report that overexpression of p27Kip1 triggers apoptosis in several different human cancer cell lines. Using a recombinant adenoviral vector that expresses p27Kip1 (Adp27), we found that overexpression of p27Kip1 in MDA-MB-231 breast cancer cells induces apoptosis that was seen by a number of different techniques, including flow cytometry and in situ terminal deoxynucleotidyl transferase-mediated nick end labeling, flow cytometric assay for sub-G1 population, and 4',6-diamindino-2-phenylindole staining. Cleavage of poly(ADP-ribose) polymerase and degradation of cyclin B1, events that are known to be associated with apoptosis, were also observed following overexpression of p27Kip1. This is the first report indicating a role for p27Kip1 in induction of apoptosis.
Katayose
Y
Y
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Kim
M
M
Rakkar
A N
AN
Li
Z
Z
Cowan
K H
KH
Seth
P
P
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011065:Poly(ADP-ribose) Polymerases