AATF

AATF Full Name

apoptosis antagonizing transcription factor

AATF Introduction

Apoptosis antagonizing transcription factor (AATF), frequently referred to in scientific literature as Che-1, is a highly conserved, multidomain nuclear protein originally identified as an RNA polymerase II-interacting factor. Characterized by its unique nucleolar and nucleoplasmic localization, AATF/Che-1 functions as a remarkably versatile transcriptional cofactor and multivalent molecular adaptor. It lacks intrinsic DNA-binding enzymatic activity; instead, it bridges specific transcription factors with the general transcriptional machinery, acting as a central hub that coordinates gene expression, ribosome biogenesis, and cellular responses to stress.

Figure 1. Schematic representation of the AATF/Che-1 protein structure. (Source: Kaiser RWJ, et al. 2020)

AATF is a master regulator of the cellular DNA damage response (DDR) and a potent inhibitor of programmed cell death. Upon genotoxic stress, AATF is rapidly phosphorylated by key upstream kinases and recruited to sites of DNA damage. Its most defining mechanistic role lies in its direct interaction with the tumor suppressor p53. By binding to p53, AATF effectively represses p53-driven transcription of pro-apoptotic genes while simultaneously promoting the expression of cell-cycle arrest and DNA repair genes. Furthermore, AATF directly stimulates RNA polymerase I and II, sustaining cellular proliferation, modulating chromatin remodeling through histone deacetylase (HDAC) displacement, and ultimately tipping the cellular balance heavily toward survival rather than apoptosis.

Clinically, the profound anti-apoptotic and pro-proliferative capabilities of AATF intimately link its dysregulation to severe human malignancies. AATF functions essentially as a powerful oncogene in a wide array of cancers, including multiple myeloma, leukemia, neuroblastoma, and various solid tumors such as colon, lung, and breast carcinomas. In these oncological contexts, AATF is frequently overexpressed or genomically amplified, conferring aggressive tumor growth, enhanced resistance to chemotherapeutic agents, and poor patient prognosis. Because it is indispensable for the survival of tumor cells—particularly those heavily dependent on mutant p53 "gain-of-function" activities—AATF has recently emerged as a highly attractive, albeit challenging, molecular target for novel anti-cancer therapies.

Alternate Names for AATF

AATF; apoptosis antagonizing transcription factor; protein AATF; CHE 1; CHE1; DED; rb-binding protein Che-1; apoptosis-antagonizing transcription factor; CHE-1;

• 1. Kaiser RWJ, et al. AATF/Che-1-An RNA Binding Protein at the Nexus of DNA Damage Response and Ribosome Biogenesis. Front Oncol. 2020 Jun 10;10:919.
  2. Iezzi S, et al. Discovering Che-1/AATF: a new attractive target for cancer therapy. Front Genet. 2015 Apr 10;6:141.