Trafficking of the bZIP transmembrane transcription factor CREB‐H into alternate pathways of ERAD and stress‐regulated intramembrane proteolysis
D Bailey, C Barreca, P O'Hare - Traffic, 2007 - Wiley Online Library
D Bailey, C Barreca, P O'Hare
Traffic, 2007•Wiley Online LibraryCREB‐H is an ATF6‐related, transmembrane transcription factor that, in response to
endoplasmic reticulum (ER)‐associated stress, is cleaved by Golgi proteases and
transported to the nucleus to effect appropriate adaptive responses. We characterize the ER
processing and turnover of CREB‐H with results which have important implications for ER
stress regulation and signalling. We show that CREB‐H is glycosylated and demonstrate
that both the ER and nuclear forms of CREB‐H have short half‐lives. We also show that …
endoplasmic reticulum (ER)‐associated stress, is cleaved by Golgi proteases and
transported to the nucleus to effect appropriate adaptive responses. We characterize the ER
processing and turnover of CREB‐H with results which have important implications for ER
stress regulation and signalling. We show that CREB‐H is glycosylated and demonstrate
that both the ER and nuclear forms of CREB‐H have short half‐lives. We also show that …
CREB‐H is an ATF6‐related, transmembrane transcription factor that, in response to endoplasmic reticulum (ER)‐associated stress, is cleaved by Golgi proteases and transported to the nucleus to effect appropriate adaptive responses. We characterize the ER processing and turnover of CREB‐H with results which have important implications for ER stress regulation and signalling. We show that CREB‐H is glycosylated and demonstrate that both the ER and nuclear forms of CREB‐H have short half‐lives. We also show that CREB‐H is subject to cycles of retrotranslocation, deglycosylation and degradation through the ER‐associated degradation (ERAD) pathway. Proteasome inhibition resulted in accumulation of a cytosolic intermediate but additionally, in contrast to inhibition of glycosylation, promoted specific cleavage of CREB‐H and nuclear transport of the N‐terminal‐truncated product. Our data indicate that under normal conditions CREB‐H is transported back from the ER to the cytosol, where it is subject to ERAD, but under conditions that repress proteasome function or promote load CREB‐H is diverted from this pathway instead undergoing cleavage and nuclear transport. Finally, we identify a cytoplasmic determinant involved in CREB‐H ER retention, deletion of which results in constitutive Golgi transport and corresponding cleavage. We present a model where cellular stresses may be sensed at different levels by different members of the basic and leucine zipper domain transmembrane proteins.
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