How is ATF6 activated?
ATF6 has been implicated in the endoplasmic reticulum (ER) stress response pathway since it can activate expression of GRP78 and other genes induced by the ER stress response. ER stress appears to activate ATF6 by cleavage from the ER membrane and translocation to the nucleus.
What is the function of ATF6?
The role of activating transcription factor 6 in hydroxycamptothecin-induced fibroblast autophagy and apoptosis. OTUB1 facilitates bladder cancer progression by stabilizing ATF6 in response to endoplasmic reticulum stress. Atf-6 Regulates Lifespan through ER-Mitochondrial Calcium Homeostasis.
Where is ATF6 released from?
Upon sensing ER stress, ATF6 family members are released from the ER and traffic to the Golgi apparatus where they encounter two proteases, site-1 and site-2 proteases respectively.
Where is ATF6 cleaved?
the Golgi apparatus
ATF6 Signaling
During ER stress, dissociation of BiP causes ATF6 export to the Golgi apparatus, where it is cleaved by the proteases site-1 protease (S1P) and site-2 protease (S2P) to liberate its transcriptionally active cytosolic domain [15].
Is ATF6 a protein?
Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ATF6 gene and is involved in the unfolded protein response.
Does UPR decrease protein synthesis?
The unfolded protein response (UPR) is an adaptive cellular response that aims to relieve endoplasmic reticulum (ER) stress via several mechanisms, including inhibition of protein synthesis and enhancement of protein folding and degradation.
What is perk protein?
Background: Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is a type I transmembrane protein that functions as an endoplasmic reticulum (ER) stress sensor to regulate global protein synthesis.
What are the two main mechanisms used by the UPR to regulate cellular processes?
The two principal UPR receptors involved are Ire1 and PERK. By binding with the protein TRAF2, Ire1 activates a JNK signaling pathway, at which point human procaspase 4 is believed to cause apoptosis by activating downstream caspases.
What activates UPR?
The UPR is activated when unfolded proteins accumulate in the endoplasmic reticulum. This accumulation puts a greater load on the molecules in charge of folding the proteins, and therefore the UPR works to balance this by lowering the number of unfolded proteins present in the cell.
What are the three main categories of cellular processes that are regulated by the UPR?
The UPR involves three signaling pathways governed by three integral ER membrane proteins: PERK (protein kinase-like ER kinase, pancreatic ER eukaryotic translation initiation factor (eIF)-2a kinase; official name: EIF2AK3), IRE-1 (inositol-requiring protein 1; official name: ERN1), and ATF6 (activating transcription …
What is UPR pathway?
Eukaryotic cells possess a highly conserved signaling pathway, termed the unfolded protein response (UPR), to adapt and respond to ER stress conditions, thereby promoting cell survival.
Why is the unfolded protein response important?
The unfolded protein response (UPR) is an intracellular signal transduction pathway that monitors endoplasmic reticulum (ER) homeostasis. Activation of the UPR is required to alleviate the effects of ER stress. However, our understanding of what physiologically constitutes ER stress or disequilibrium is incomplete.
Which organelle is responsible for UPR?
The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade, the unfolded protein response (UPR), is activated.