TY - JOUR
T1 - A novel apoptosis pathway activated by the carboxyl terminus of p21
AU - Dong, Chen
AU - Li, Qing
AU - Lyu, Shu Chen
AU - Krensky, Alan M.
AU - Clayberger, Carol
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/2/1
Y1 - 2005/2/1
N2 - Delivery of biologically active peptides into cells may help elucidate intracellular signal transduction pathways, identify additional in vivo functions, and develop new therapeutics. Although p21 was first identified as a major regulator of cell cycle progression, it is now clear that p21 subserves multiple functions. The amino terminus of p21 interacts with cyclins and cyclin-dependent kinases, while the carboxyl terminus interacts with proliferating cell nuclear antigen (PCNA), growth arrest and DNA damage-inducible gene 45 (GADD45), calmodulin, SET, and CCAAT/enhancer binding protein-α (C/ EBP-α). A chimeric peptide, p21-IRS, consisting of the carboxyl terminal domain of p21 conjugated to a pentapeptide (RYIRS) rapidly enters lymphoid cells and activates apoptosis. In the present study, we investigate the molecular events involved in p21-activated apoptosis. Comparison of p21-IRS with other known proapoptotic agents demonstrates that p21-IRS activates a novel apoptotic pathway: mitochondria are central to the process, but caspases and a decrease in ΔΨm are not involved. Targeting the p21 peptide to specific cell populations may allow development of novel therapies to eliminate aberrant cells in human diseases.
AB - Delivery of biologically active peptides into cells may help elucidate intracellular signal transduction pathways, identify additional in vivo functions, and develop new therapeutics. Although p21 was first identified as a major regulator of cell cycle progression, it is now clear that p21 subserves multiple functions. The amino terminus of p21 interacts with cyclins and cyclin-dependent kinases, while the carboxyl terminus interacts with proliferating cell nuclear antigen (PCNA), growth arrest and DNA damage-inducible gene 45 (GADD45), calmodulin, SET, and CCAAT/enhancer binding protein-α (C/ EBP-α). A chimeric peptide, p21-IRS, consisting of the carboxyl terminal domain of p21 conjugated to a pentapeptide (RYIRS) rapidly enters lymphoid cells and activates apoptosis. In the present study, we investigate the molecular events involved in p21-activated apoptosis. Comparison of p21-IRS with other known proapoptotic agents demonstrates that p21-IRS activates a novel apoptotic pathway: mitochondria are central to the process, but caspases and a decrease in ΔΨm are not involved. Targeting the p21 peptide to specific cell populations may allow development of novel therapies to eliminate aberrant cells in human diseases.
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U2 - 10.1182/blood-2004-06-2188
DO - 10.1182/blood-2004-06-2188
M3 - Article
C2 - 15466931
AN - SCOPUS:12844262761
VL - 105
SP - 1187
EP - 1194
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -