iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53.
iASPP is one of the most evolutionarily conserved inhibitors of p53, whereas ASPP1 and ASPP2 are activators of p53. We show here that, in addition to the DNA-binding domain, the ASPP family members also bind to the proline-rich region of p53, which contains the most common p53 polymorphism at codon 72. Furthermore, the ASPP family members, particularly iASPP, bind to and regulate the activity of p53Pro72 more efficiently than that of p53Arg72. Hence, escape from negative regulation by iASPP is a newly identified mechanism by which p53Arg72 activates apoptosis more efficiently than p53Pro72.
Bergamaschi
Daniele
D
Ludwig Institute for Cancer Research, University College London, 91 Riding House Street, London W1W 7BS, UK.
Samuels
Yardena
Y
Sullivan
Alexandra
A
Zvelebil
Marketa
M
Breyssens
Hilde
H
Bisso
Andrea
A
Del Sal
Giannino
G
Syed
Nelofer
N
Smith
Paul
P
Gasco
Milena
M
Crook
Tim
T
Lu
Xin
X
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D001120:Arginine; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics; D002277:Carcinoma / Q000235:genetics; D002478:Cells, Cultured; D003062:Codon; D017124:Conserved Sequence; D005260:Female; D005786:Gene Expression Regulation; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011392:Proline / Q000378:metabolism*; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D003062:Codon; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014443:Tyrosine; D001120:Arginine; D011392:Proline