The ATF6 pathway Sample Clauses

The ATF6 pathway. ATF6 is a type II ER transmembrane protein with a luminal C-terminus that contains a Golgi localization signal (Shen et al., 2002). In unstressed cells BiP/GRP78 masks the Golgi localization signal, but in the presence of unfolded proteins BiP/GRP78 dissociates from ATF6, unmasking the Golgi localisation signal and permitting trafficking to the Golgi apparatus (Haze et al., 1999; Xxxx et al., 2002; Breckenridge et al., 2003; Xxxx and Xxxxxx, 2005; Xxxx et al., 2005). Upon arrival at the Golgi complex ATF6 is sequentially cleaved by two proteases (Xxxx et al., 1999). The processed forms of ATF6 translocate to the nucleus acting as transcription factors and upregulate the transcription of several UPR genes such as the chaperones BiP/GRP78 and Homocystein- responsive endoplasmic reticulum-resident ubiquitin-like domain member-1 (Herp) (Xxxxxx et al., 2001; Xxxxxxxx et al., 2004; Xxxxxxxx et al., 2007). Mammals have two ATF6 isoforms, ATF6α and ATF6β (Xxxx and Xxxxxx, 2005; Xxxxx et al., 2013). ATF6α has an N-terminal transactivation domain which increases ATF6α transcriptional activity (Xxxxxxxx et al., 2002; Xxxxxxxx et al., 2004). ATF6β functions as a negative regulator of ATF6α (Xxxxxxxx et al., 2004; Xxxxxxxx et al., 2007). ATF6α is a potent but transient transcription factor responsible for a coordinated transcriptional induction of ER chaperones (Xxxxxxxx et al., 2002; Xxx and Xxxxxx, 2007).