ER signal

Unfolded protein response, when mis-folded proteins accumulate in the ER, signal transduction pathways are activated that increase the biosynthetic capacity and decrease the biosynthetic burden of the ER. 

The discovery of structurally novel SERMs continues to provide insights into the complexities of ER signaling. Chemical tools have been developed to test clinical hypotheses that SERMs may be used to treat a variety of diseases ranging from... 

One approach to interfere with ER signalling is to reduce the circulating level of its ligand estradiol by inhibiting the enzyme aromatase. Aromatisation is the last step in the synthesis of estradiol. This reaction is catalysed by the P450 aromatase mono-oxygenase complex that is present in the smooth endoplasmic... 

Selective control configurations also require external feedback to protect them from reset windup. Part (d) has a combination of selective and cascade systems and in such configuration, the external reset (ER) signal (not shown) is taken from the measurement of the slave controller (FRC). 

Figure 13.1. Functional domains of UGT1A proteins and multigene organization. UGT1A family proteins contain ER signal sequence at the N-terminus, followed by a divergent region and a common region at the C-terminus.

This scheme represents the regulatory events governed by ER signaling pathways which occur mainly in the ER and the nucleus and, to a lesser extend, in the Golgi apparatus. It indicates also some phenotypic aspects such as the induction of apoptosis under prolonged ER stress which most likely represents another important aspect of ER stress signaling but at the sub-cellular level. 

The hydrophobic core of ER signal sequences is essential for their function. For Instance, the specific deletion of several of the hydrophobic amino acids from a signal sequence, or the introduction of charged amino acids into the hydrophobic core by mutation, can abolish the ability of the N-termlnus of a protein to function as a signal sequence. As a consequence, the modified protein remains in the cytosol, unable to cross the ER membrane into the lumen. Using recombinant DNA techniques, researchers have produced cytosolic proteins with added N-termlnal amino acid sequences. Provided the added sequence is sufficiently long and hydrophobic, such a modified cytosolic protein is translocated to the ER lumen. Thus the hydrophobic residues... 

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