Transcription Factor ATF5 Dynamics in Cancer and Cellular Differentiation

Activating Transcription Factor 5 (ATF5) is a member of the basic leucine zipper family that orchestrates cellular stress responses, promotes survival programmes and modulates differentiation pathways. In normal development, ATF5 expression peaks transiently to govern lineage specification, particularly within neural and cartilage progenitors, by regulating anti-apoptotic genes such as MCL1 and influencing endoplasmic reticulum homeostasis. Tumour cells co-opt ATF5’s prosurvival function to withstand environmental stress, evade programmed cell death and sustain proliferation. Elevated ATF5 levels have been observed across glioblastoma, breast and other solid tumours, where it stabilises BCL-2 family members and interacts with molecular chaperones to resist proteotoxic and genotoxic damage. The dynamic regulation of ATF5—via transcriptional control, post-translational modifications and protein–protein interactions—underpins its dual role in driving lineage fidelity in development and enabling oncogenic adaptation. Recent efforts have thus focused on dissecting its molecular partners, mapping its downstream transcriptional network and developing inhibitory strategies to disrupt ATF5-dependent survival in cancer cells without compromising normal tissue differentiation.

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Transcription Factor ATF5 Dynamics in Cancer and Cellular Differentiation publication trend

The graph below shows the total number of articles in transcription factor atf5 dynamics in cancer and cellular differentiation across all publications each year (not limited to Nature Index journals).

Technical terms

Transcription factor: A protein that binds to specific DNA sequences to regulate gene expression.

Basic leucine zipper (bZIP): A structural motif enabling dimerisation and DNA binding, characteristic of ATF family members.

Dominant-negative mutant: An engineered variant that interferes with normal protein function by forming inactive complexes.

Cell-penetrating peptide: A short sequence facilitating delivery of therapeutic cargo across cellular membranes.

Apoptosis: Programmed cell death characterised by biochemical and morphological changes, essential for tissue homeostasis.

References

1. Targeting Transcription Factors ATF5, CEBPB and CEBPD with Cell-Penetrating Peptides to Treat Brain and Other Cancers. Cells (2023).
2. Dpep Inhibits Cancer Cell Growth and Survival via Shared and Context-Dependent Transcriptome Perturbations. Cancers (2023).
3. The transcription factor ATF5: role in cellular differentiation, stress responses, and cancer. Oncotarget (2017).
4. Advancements in Activating Transcription Factor 5 Function in Regulating Cell Stress and Survival. International Journal of Molecular Sciences (2022).
5. BCL-2 Is a Downstream Target of ATF5 That Mediates the Prosurvival Function of ATF5 in a Cell Type-dependent Manner*. Journal of Biological Chemistry (2011).
6. HSP70 Protein Promotes Survival of C6 and U87 Glioma Cells by Inhibition of ATF5 Degradation*. Journal of Biological Chemistry (2011).
7. The Endoplasmic Reticulum Stress Transducer BBF2H7 Suppresses Apoptosis by Activating the ATF5-MCL1 Pathway in Growth Plate Cartilage*. Journal of Biological Chemistry (2012).