Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis.

EMBO Reports
Lin YuanLingqiang Zhang

Abstract

The KRAB-type zinc-finger protein Apak was recently identified as a negative regulator of p53-mediated apoptosis. However, the mechanism of this selective regulation is not fully understood. Here, we show that Apak recognizes the TCTTN2−30TTGT consensus sequence through its zinc-fingers. This sequence is specifically found in intron 1 of the proapoptotic p53 target gene p53AIP1 and largely overlaps with the p53-binding sequence. Apak competes with p53 for binding to this site to inhibit p53AIP1 expression. Upon DNA damage, Apak dissociates from the DNA, which abolishes its inhibitory effect on p53-mediated apoptosis.

References

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Citations

Dec 10, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Hideya IgarashiKatsuhiko Ishihara
Apr 3, 2014·Cellular Oncology (Dordrecht)·Ioannis A Voutsadakis
Mar 17, 2012·EMBO Reports·Débora Rosa Bublik, Moshe Oren
Apr 5, 2014·Nucleus·Francesca R Santoni de Sio
Mar 7, 2021·International Journal of Molecular Sciences·Joanna SobocińskaUrszula Oleksiewicz

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis