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Review
. 2020 May 15;80(10):1905-1911.
doi: 10.1158/0008-5472.CAN-19-3652. Epub 2020 Feb 24.

_targeting the SAGA and ATAC Transcriptional Coactivator Complexes in MYC-Driven Cancers

Lisa Maria Mustachio  1   2 , Jason Roszik  3   4 , Aimee Farria  1   2   5 , Sharon Y R Dent  6   2   5
Affiliations
Review

_targeting the SAGA and ATAC Transcriptional Coactivator Complexes in MYC-Driven Cancers

Lisa Maria Mustachio et al. Cancer Res. .

Abstract

_targeting epigenetic regulators, such as histone-modifying enzymes, provides novel strategies for cancer therapy. The GCN5 lysine acetyltransferase (KAT) functions together with MYC both during normal development and in oncogenesis. As transcription factors, MYC family members are difficult to _target with small-molecule inhibitors, but the acetyltransferase domain and the bromodomain in GCN5 might provide alternative _targets for disruption of MYC-driven functions. GCN5 is part of two distinct multiprotein histone-modifying complexes, SAGA and ATAC. This review summarizes key findings on the roles of SAGA and ATAC in embryo development and in cancer to better understand the functional relationships of these complexes with MYC family members, as well as their future potential as therapeutic _targets.

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Conflict of interest statement

Disclosure of Conflicts of Interest

The authors have declared that no competing interest exists.

Figures

Figure 1.
Figure 1.. _targeting SAGA and ATAC in cancer.
A. GCN5 mRNA levels are significantly upregulated in most human cancers (red) relative to adjacent normal tissues (green), as indicated by analysis of The Cancer Genome Atlas (*, P<0.05; **, P<0.01; ***, P<0.001). Multiple cancer types show dependencies on B. GCN5 and USP22 as well as C. YEATS2 and ATAC2, as shown by DepMap, where a lower CERES score indicates that a gene is essential to a cell line, where a score of 0 indicates that the gene is not critical. Cell lines containing damaging, hotspot or other non-conserving mutations in YEATS2 or ATAC2 are highlighted in red, orange and blue, respectively. D. Model summarizing how SAGA components promote MYC functions, through acting as a coactivator for MYC _target genes and by increasing the stability of MYC protein through acetylation (GCN5) and deubiquitination (USP22).
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