Che1/AATF interacts with subunits of the histone acetyltransferase core module of SAGA complexes

Abstract

General Control Non-derepressible 5 (GCN5) and Alteration/Deficiency in Activation 2 and 3 proteins (ADA2 and ADA3, respectively) are subunits of the Histone AcetylTransferase (HAT) module of SAGA- and ATAC-type co-activators. We previously reported four new interacting partners of human ADA3 identified by screening a human fetal brain cDNA library using yeast two hybrid technology. One of these partners was Apoptosis-Antagonizing Transcription Factor (AATF), also known as Che-1, an RNA polymerase II-binding protein with a number of roles in different cellular processes including regulation of transcription, cell proliferation, cell cycle control, DNA damage responses and apoptosis. Che-1/AATF is a potential therapeutic target for cancer treatments. In this study, we aimed to identify whether besides ADA3, other components of the HAT modules of SAGA and ATAC complexes, human ADA2 and GCN5 also interact with Che-1/AATF. Co-immunoprecipitation and co-localization experiments were used to demonstrate association of AATF both with two ADA2 isoforms, ADA2A and ADA2B and with GCN5 proteins in human cells and yeast two-hybrid assays to delineate domains in the ADA2 and GCN5 proteins required for these interactions. These findings provide new insights into the pathways regulated by ADA-containing protein complexes.

Che-1/AATF-induced transcriptionally active chromatin promotes cell proliferation in multiple myeloma

“…Che-1 is known to interact with several components of histone acetyltransferase complexes. 17,18 Herein, we broadly estimate whether Che-1 was required for correct histone acetylation on different lysine residues by performing a mass spectrometry analysis quantifying the majority of histone modifications in Che-1-depleted or not Kms27 cells. Because Che-1 depletion induces apoptosis in MM cells, 23 all subsequent analyses were performed 48 hours after small interfering RNA (siRNA) Che-1 transfection or doxycycline treatment (shChe-1 activation), when the apoptotic process was not yet activated (supplemental Figure 2A-C).…”

“…12 Several studies have described the involvement of Che-1 in the regulation of gene transcription and tumor cell proliferation. [13][14][15][16] It is present in the histone acetyltransferase complexes SAGA and ATAC through its interaction with the transcriptional coactivators ADA2, ADA3, and GCN5, 17,18 and it acts as an endogenous histone deacetylase 1 (HDAC1) inhibitor through its ability to disrupt the binding of pRb and Sp1 proteins to this enzyme. 13,19 In addition, Che-1 plays an important role in the cellular response to DNA damage or to other cellular stressors, [20][21][22] and it sustains cell survival in MM cells by inhibiting mTORC1 activity and inducing autophagy.…”

Retracted: The PI3K/AKT axis modulates AATF activity in Wilms’ tumor cells

“…At the same time, AATF plays a role in such processes as proliferation, stress reactions to DNA injury, and regulation of the cell cycle . AATF is crucial in stress reactions related to DNA injury, such as the stimulation of p53 and, possibly, p21 . Excessive AATF expression is present in some human leukemic cells .…”

“…Transcription factors (TFs) such as apoptosis‐antagonizing transcription factor (AATF, also known as TRB), are specific to RNA polymerase II, indicating their modulation of cell death . At the same time, AATF plays a role in such processes as proliferation, stress reactions to DNA injury, and regulation of the cell cycle . AATF is crucial in stress reactions related to DNA injury, such as the stimulation of p53 and, possibly, p21 .…”

Advances and Opportunities in Epigenetic Chemical Biology

“…Methods that have been used to investigate protein-protein interactions in histones and histone-modifying enzymes range from two-hybrid selection systems [282][283][284] and fluorescence techniques [285,286] to proximity-induced labelling, [287,288] to name a few. Among the many proximity-dependent methods available to investigate these interactions, a classic approach involves the use of chemical crosslinkers to elucidate points of interaction as well as novel interacting proteins.…”