Human Sgo1 is an excellent target for induction of apoptosis of transformed cells.
Aneuploidy, a frequent form of genomic instability, is a direct result of mis-segregation of sister chromatids during mitosis. Cohesion of sister chromatids in eukaryotes is primarily achieved by the cohesin complex. Since Sgo1 functions to protect centromeric cohesin and since depletion of Sgo1 results in precocious chromosomal segregation and massive mitotic arrest, we reasoned that disruption of Sgo1 functions by delivery of a competitive peptide could interfere with normal cell cycle progression. Treatment of HeLa and A549 cells with a Sgo1 fragment of 22 amino acids (corresponding to a conserved basic region at the C-terminus) linked with a cell-permeable peptide penetratin, but not with penetratin alone, resulted in concentration-dependent suppression of viability. Following 24 h treatment with Sgo1 peptide at a 40 muM final concentration, HeLa cell viability was dramatically reduced. The Sgo1 peptide induced rapid and drastic changes of cell and nuclear morphologies, which were associated with disappearance of cellular Sgo1 at kinetochores in mitotic cells. Moreover, the reduction in HeLa cell viability after treatment with Sgo1 peptide resulted from induction of apoptosis. Interestingly, WI-38 diploid fibroblasts were rather resistant to the treatment with Sgo1 peptide. These normal cells exhibited little changes of cellular and nuclear morphologies, and remained viable after exposure to 40 muM of Sgo1 peptide for 24 h. Our combined studies thus suggest that small peptides corresponding to conserved regions of Sgo1 are capable of functioning as dominant negative inhibitors in vivo and that Sgo1 is an excellent target for induction of apoptosis of cancer cells.
Yang
Yali
Y
Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China.
Wang
Xiaoxing
X
Dai
Wei
W
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000502:physiology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D018797:Cell Cycle Proteins; D010455:Peptides; C496644:SGO1 protein, human