Che-1 (protein AATF, apoptosis-antagonizing transcription factor) is a widely expressed nuclear protein that belongs to the AATF family. Hyperphosphorylated during the G1/S phase transition, Che-1 may function as a general inhibitor of the histone deacetylase HDAC1. Che-1 binding to the pocket region of Rb may displace HDAC1 from Rb/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Displacement of HDAC1 from Sp1 bound to the p21 promoter leads to increased expression of Che-1. It also antagonizes PAR4 (prostate apoptosis response 4) mediated induction of aberrant amyloid peptide production in Alzheimer disease (AD; presenile and senile dementia). PAR4 is a leucine zipper protein that is pro-apoptotic and associated with neuronal degeneration in AD. Che-1 interaction with
PAR4 suggests that it might directly or indirectly participate in regulation of PAR4 activity. Che-1 also co-localizes with PAR4 in both cytoplasmic and nuclear compartments, and it interacts directly and selectively with PAR4 via the leucine zipper domain in neural cells.