ATF-5 Activators

Activating Transcription Factor 5 (ATF-5) is a member of the ATF/CREB family of transcription factors, playing a critical role in cellular stress response, survival, and differentiation. It is ubiquitously expressed across various tissues, with notable roles in the nervous system, where it supports neuronal survival and function. ATF-5 is involved in regulating the expression of genes critical for cellular adaptation to environmental stresses, such as nutrient deprivation or oxidative stress, and contributes to the maintenance of cellular homeostasis. Its activation is pivotal for the initiation of transcriptional programs that promote cell survival under adverse conditions, making it a key player in determining cell fate during stress responses. Furthermore, ATF-5 is implicated in the regulation of proliferation and differentiation in several cell types, including its role in the development and maintenance of cancer cells, highlighting its importance in both physiological and pathological processes.

The activation of ATF-5 is mediated through various signaling pathways that respond to cellular stress and environmental cues. One primary mechanism involves the integrated stress response (ISR), where ATF-5 is upregulated in response to endoplasmic reticulum (ER) stress, amino acid deprivation, or oxidative stress. This upregulation is typically mediated through the activation of upstream kinases, such as PERK (protein kinase RNA-like endoplasmic reticulum kinase), which phosphorylate eukaryotic initiation factor 2α (eIF2α), leading to an attenuation of general protein synthesis but selective translation of ATF-5 mRNA. Additionally, other signaling molecules, including the mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), can influence ATF-5 activity by modulating its expression levels or promoting its nuclear translocation, thereby affecting its transcriptional activity. The activation of ATF-5 enables cells to initiate specific gene expression programs that support adaptation and survival under stress conditions. This complex regulatory network ensures that ATF-5 activation is tightly controlled, allowing cells to efficiently respond to and survive environmental challenges.