Calnexin Controls the STAT3-Mediated Transcriptional Response to EGF

Calnexin is a well-characterized transnnembrane chaperone involved in the folding of newly synthesized glycoproteins in the lumen of the endoplasmic reticulum (ER). Here, we reveal a previously unrecognized function of calnexin in regulating the transcriptional response downstream of epidermal growth factor receptor (EGF), the product of a well-known human oncogene. We find that cell stimulation with EGF leads to the caspase-8-dependent cleavage of the calnexin cytoplasmic domain, preferentially at ER-mitochondria interaction sites. The released fragment translocates into the nucleus, binds to PIAS3-a natural inhibitor of activated STAT3-and, thus, acts as an enhancer of the STAT3-mediated transcriptional response to EGF. Also, we reveal the unsuspected capacity of calnexin to sense ER stress and, in response, prevent the EGF-induced processing of its cytosolic domain. Thus, cells integrate the health status of the ER to determine the amplitude of their response to EGF.


Published in:
Molecular Cell, 51, 3, 386-396
Year:
2013
Publisher:
Cambridge, Elsevier
ISSN:
1097-2765
Laboratories:


Note: The status of this file is: Involved Laboratories Only


 Record created 2013-10-01, last modified 2018-03-17

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