How is XBP1 splicing related to the UPR?
XBP1 is a major regulator of UPR, mediating adaptation to ER stress. XBP1 has two isoforms, i.e. XBP1 spliced (s) and XBP1 unspliced (u). XBP1s is a key transcriptional factor that regulates the transcription of genes involved in UPR. XBP1u is an inactivate form with no transcriptional activity11.
What is IRE1 Alpha?
The IRE1 alpha protein is a single-pass, type I membrane protein within the ER that functions as a sensor of unfolded ER proteins. It is ubiquitously expressed, with highest levels notably in the pancreas. IRE1 alpha autophosphorylates and under ER stress conditions, is ADP-ribosylated by the protein PARP16.
Is chop a protein?
CHOP belongs to the family of CCAAT/enhancer binding proteins (C/EBPs) and is involved in the regulation of genes that encode proteins involved in proliferation, differentiation and expression, and energy metabolism. CHOP is a 29 kD protein with 169 (human) or 168 (rodents) amino acid residues.
What do ER chaperones do?
ER chaperones and folding enzymes ensure proper conformational maturation of nascent secretory proteins in a process that is deemed ER protein QC 10. The ER protein QC system closely monitors protein folding using specific factors that assist newly synthesized proteins to achieve their final conformation.
What happens if endoplasmic reticulum is absent?
If the ER is absent, the skeletal muscle fibers would not be able to contract muscles. Consequently, in the absence of all these basic and essential cellular activities, the cells tend to die.
What is the function of IRE1 in the cell?
IRE1/ERN1 (Inositol-Requiring Enzyme 1/Endoplasmic Reticulum to Nucleus 1) is the most evolutionarily conserved endoplasmic reticulum membrane resident protein. It is involved in multiple cellular processes and regulates both cell survival and cell death.
What is Ridd in biology?
Other than splicing XBP1 mRNA, the RNase of IRE1 can rapidly cleave a subset of mRNAs and so halts the production of proteins that challenge the ER. This mechanism is known as regulated IRE1-dependent decay (RIDD; Hollien and Weissman, 2006).
What protein causes apoptosis?
P53 gene. The tumor suppressor gene p53 is a gene with a key role in apoptosis. The protein it codes for belongs to a family of proteins that has three members: P53, P63 and P73. All of them have about 60-70% amino-acid identity of the DNA-binding region and all three can induce apoptosis38.
What is C EBP homologous protein?
C/EBP homologous protein is a cellular stress sensor that can be induced in response to a series of physiological or stress conditions such as ER stress, nutrient deprivation, DNA damage, cellular growth arrest, and hypoxia (1, 2, 24).
What is the role of chaperones in protein folding?
Chaperones are proteins that guide proteins along the proper pathways for folding. They protect proteins when they are in the process of folding, shielding them from other proteins that might bind and hinder the process.
Are there chaperones in endoplasmic reticulum?
The chaperones of the ER are critical to many aspects of ER function, whether in protein folding modes, as calcium binders, as sensors of stress such as the unfolded protein response (10), or due to cell-surface localization or extracellular release, as immune modulators (11–18).
What is the difference between binding sites and active sites?
This specific region also has a binding site along with a catalytic site. Therefore, binding sites aid only in the binding of a ligand to a large molecule whereas active sites aid both the binding of a ligand to a large molecule while letting it undergo a catalyzed chemical reaction.
What is the function of XBP1?
Moreover, studies have shown that XBP1s regulates the transcription of diverse genes that are involved in lipid and glucose metabolism and immune responses. Therefore, XBP1s has been considered an important therapeutic target in studying various diseases, including cancer, diabetes, and autoimmune and inflammatory diseases.
Is XBP-1 required for biogenesis of cellular secretory machinery of exocrine glands?
Lee A.-H., Chu G.C., Iwakoshi N.N., Glimcher L.H. XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands. EMBO J. 2005;24:4368–4380. doi: 10.1038/sj.emboj.7600903.
What is the difference between XBP1 and xbp1mrna?
Xbp1mRNA usually encodes an unstable protein XBP1u (unspliced form XBP1, 267 amino acids in mice), whereas spliced mRNA is translated into XBP1s (371 amino acids) by a frameshift [19].
