Background
ATF6 is a constitutively expressed, endoplasmic reticulum (ER) membrane-anchored transcription factor.  ATF6 is a key transcriptional activator of the unfolded protein response (UPR), which allows mammalian cells to maintain cellular homeostasis when they are subjected to environmental and physiological stresses that target the ER (reviewed in Shen and Prywes, and Groenendyk and Michalak). The C-terminus of ATF6 is located in the ER lumen and its N-terminal DNA binding domain faces the cytosol. AFT6 plays a key role in the ER stress response by transmitting the ER stress signal across the ER membrane into the nucleus.  The induction of new gene expression by ATF6 is an important aspect of the ER stress response. In response to certain stress conditions, ATF6 translocates from the ER to the Golgi.  The 90 kDa full-length ATF6 is processed within the Golgi to its active 50 kDa form through sequential cleavage by site-1 and site-2 proteases (S1P and S2P). Proteolytic activation of ATF6 in the ER stress response is a mechanism to regulate membrane-bound factors, and is referred to as regulated intramembrane proteolysis. The N-terminal active ATF6 translocates to the nucleus where it binds to ER stress-response elements in ER stress-response genes (ERSRGs). ATF6 is a potent transcriptional activator of ERSRGs. The fully glycosylated form of ATF6, a 670 amino acid protein, exhibits an electrophoretic mobility of ~90 kDa in denaturing SDS-gels, in part because of the glycosylated modifications.  ATF6 has 3 consensus sites for N-linked glycosylation and exists constitutively as a glycosylated protein.  Differentially glycosylated ATF6 forms may result from mutations or experimental treatment (Shen and Prywes, 2005).

Antigen
This monoclonal antibody was made against a partial protein containing amino acids 1-273 of human ATF6.

Application Notes
(1) The ATF6 (IMG-273) has been cited to recognize both full-length and cleaved forms of ATF6. Please refer to the references in the Product Citation list for more comprehensive information.

(2) The ATF6 transfected cell lysate (40210) is recommended as a useful western blot positive control to run in parallel with your experimental samples.

(3) Active/cleaved forms of ATF6 are generated through proteolytic cleavage during ER stress. Different molecular weights have been described for cleaved forms. A sample protocol was first described in Luo and Lee (2002) wherein NIH3T3 cells were treated with the amino acid analogue azetidine (AzC), and full-length and cleaved forms ATF6 were detected with IMG-273. The results show that in addition to the major 90 kDa full length ATF6, protein bands over the range of 50-70 kDa were detectable following AzC treatment (Luo and Lee, 2002: Figure 4A, page 791).  Many protocols and other cleaved forms have been described since, please consult the literature for additional information.

(4) For immunofluorescence microscopy, cells were fixed in methanol at -20 degrees C (Thomas et al, 2005).  Thomas et al used immunofluorescence to identify ATF6 with IMG-273 in the nucleus.  

(5) The active/cleaved 50 kDa nuclear form of ATF6 using IMG-273 has been found to be strongly expressed in certain tumor cell lines derived from B cell lymphoma (DEL), primary effusion lymphoma [BC-3 (ATCC CRL-2277), PEL-SY, HBL-6], lymphoblastic leukemia (DS-1) and multiple myeloma (RPMI-8226, NCI-H929), (Jenner et al. 2003).  

(6) Cleaved 60 and 36 kDa ATF6 forms have also been described in the nucleus (Mao et al, 2007).  

(7) The ATF6 antibody is reported to be specific for ATF6a, recognizing ATF6a but not ATF6b (Bommiasamy et al, 2009).  

Genebank Info (Protein)
NP_031374

Related Products

Reference
1. Groenendyk J and M Michalak. 2005. Endoplasmic reticulum quality control and apoptosis. Acta Biochimica Polonica 52:381-295.
2. Shen J and R Prywes. 2005. ER stress signaling by regulated proteolysis of ATF6. Methods 35:382-389.

Product Citations
1. Requirement of the p38 mitogen-activated protein kinase signalling pathway for the induction of the 78kDa glucose-regulated protein/immunoglobulin heavy-chain binding protein by azetidine stress: activating transcription factor 6 as a target for stress-induced phosphorylation. Shengzhan Luo and Amy S. Lee. Biochem. J. 366 ;787–795 (2002). IMGENEX antibodies cited: 1. ATF6 (IMG-273) [WB, Fig.4 (NIH3T3 cells)].
2. Kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphoma has a plasma cell gene expression profile. Richard G. Jenner, Karine Maillard, Nicola Cattini, Robin A. Weiss, Chris Boshoff, Richard Wooster, and Paul Kellam. PNAS 2003 100: 10399-10404; published online before print as 10.1073/pnas.1630810100. IMGENEX antibodies cited: 1. ATF6 (IMG-273) [WB, Fig.2 (DLBCL derived DEL cells, PEL cells, and MM-derived cell lines)].
3. Underglycosylation of ATF6 as a Novel Sensing Mechanism for Activation of the Unfolded Protein Response. Min Hong, Shengzhan Luo, Peter Baumeister, Jen-Ming Huang, Raveen K. Gogia, Mingqing Li, and Amy S. Lee. J. Biol. Chem. 279: 11354-11363 (2004). IMGENEX antibodies cited: 1. ATF6 (IMG-273) [WB, Fig.2B (NIH3T3 cells) and Fig2D (CH0-7 cells)].
4. An SPP reporter activity assay based on the cleavage of type II membrane protein substrates provides further evidence for an inverted orientation of the SPP active site relative to presenilin. Andrew C. Nyborg, Karen Jansen, Thomas B. Ladd, Abdul Fauq, and Todd E. Golde. J. Biol. Chem., 279:43148-42156  (2004). (Western Blot, Figs 1C, 2C, 2E, 3D: Analysis of a substrate consisting of the N-terminus of ATF6 fused to a transmembrane domain suspectible to SPP cleavage in vitro)
5. 3,3'-Diindolylmethane (DIM) and derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. Abdelrahim M, K Newman, K Vanderlaag, I Samudio, and S Safe. Carcinogenesis, Dec 2005; 10.1093/carcin/bgi270. IMGENEX antibodies cited: 1. ATF6 (IMG-273) 2. DR5 (IMG-120) [WB, Fig.4 and Fig. 6 (Panc-28 cells)].
6. Involvement of a novel Q-SNARE, D12, in quality control of endomembrane system. Okumura A J, K Hatsuzawa, T Tamura, H Nagaya, K Saeki, F Okumura, K Nagao, M Nishikawa, A Yoshimura, and I Wada. J. Biol. Chem., Dec 2005; 10.1074/jbc.M509715200. IMGENEX antibodies cited: 1. ATF6 (IMG-273) [WB, Fig.5 (NIH3T3 cells)].
7. Cytoprotective gene Bi-1 is required for intrinsic protection from endoplasmic reticulum stress and ischemia-reperfusion injury. Béatrice Bailly-Maitre, Constantino Fondevila, Fady Kaldas, Nathalie Droin, Fréderic Luciano, Jean-Ehrland Ricci, Rhonda Croxton, Maryla Krajewska, Juan M. Zapata, Jerzy W. Kupiec-Weglinski, Douglas Farmer, and John C. Reed. PNAS, Feb 2006; 10.1073/pnas.0506854103. IMGENEX antibodies cited: ATF6 (IMG-273) [WB, Fig 3,5; Supportive Fig 7,11 (Hepatocyte cells)].
8. Nitric oxide induced endoplasmic reticulum stress activates the expression of cargo receptor proteins and alters the glycoprotein transport to the Golgi complex. Renna M, R Faraonio, S Bonatti, D De Stefano, R Carnuccio, G Tajana and P Remondelli., The International Journal of Biochemistry & Cell Biology, In Press, (2006) IMGENEX antibodies cited: 1. ATF6 (IMG-273) [WB, Fig.4 (DETA NONOate- and TG-treated J774 cells)].
9. Endoplasmic Reticulum Stress and Neurodegeneration in Rats Neonatally Infected with Borna Disease Virus. B. L. Williams and W. I. Lipkin. J. Virol., 80: 8613-8626 (2006). IMGENEX antibodies cited: ATF6 (IMG-273) [WB, Fig 5  (cleaved ATF6 in rat cerebellum and hippocampus tissues) ].
10. Flavivirus Infection Activates XBP1 Pathway of the Unfolded Protein Response to Cope with Endoplasmic Reticulum Stress.  Yu C-Y, Y-W Hsu, C-L Liao, and Y-L Lin. J. Virol., Sep 2006; 10.1128/JVI.00879-06. IMGENEX antibodies cited: 1. ATF6 (IMG-273) [WB, Fig.1 (N18 cells)].
11. Acetaminophen induces ER dependent signaling in mouse liver. Nagy G, T Kardon, L Wunderlich, A Szarka, A Kiss, Z Schaff, G Banheygi, J Mandl. Archives Biochemistry Biophysics. Online before print: doi:10.1016/j.abb.2006.11.021. (2007). IMGENEX antibodies cited: 1. ATF6 (IMG-273)  [WB, Fig 5 (full-length and cleaved ATF6 in mouse liver tissue) ].
12. Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase. Nyborg CN, TB Ladd, K Jansen, T Kukar and TE Golde. FASEB J. 20:1671-1679 (2006). IMGENEX antibodies cited: 1. ATF6 (IMG-273) [WB, Fig. 3C: Analysis of a substrate consisting of the N-terminus of ATF6 fused to a transmembrane domain suspectible to SPP cleavage in vitro]
13. Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutatse-1 in an ALS model. Kukuchi H, G Almer, S Yamashita, C Guegan, M Nagai, Z Xu, AA Sosunov, GM McKhann II and S Przedborski. PNAS 103:6025-6030. (2006). [Western Blots of mouse spinal cord tissue (Fig 1A: full-length and cleaved ATF6) (Fig 6 in supplemental material: cleaved ATF6) (Fig 5C: full-length ATF6 pulled down by immunoprecipition with a Bip antibody)], IF (mouse spinal cord tissues), Fig 1B.  
14. Glia-specific activation of all pathways of the unfolded protein response in vanishing white matter disease. van Kollenburg B, J van Dijk, J Garbern, AAM Thomas, GC Scheper, JM Powers, MS van der Knaap. J Neuropathol Exp Neurol., 65:707-715.  (2006). IMGENEX antibodies cited: 1. ATF6 (IMG-273) [IHC (paraffin), Fig.5A, 5G and 6D (human brain tissue sections)].
15. Reduced cell proliferation and increased apoptosis are significant pathological mechanisms in a murine model of a mild pseudoachondroplasia resuling from a mutation in the C-terminal domain of COMP. Garcia K., R Meadows, L Knowles, D Heinegard, D. Thornton, K Kadler, RP Boot-Hadford, M Briggs. Hum. Mol. Genet. 16: 2072-2088 (2007). WB: Fig 9B, density measurement of Western blots of ATF6 cleavage using tissue from the xiphoid process of mice with psuedoachondroplasia.  The authors report a 2.2 increase of cleaved ATF6 in mutant compared to normal chondrocytes.
16. Cadiomyocyte apoptosis in autoimmune cardiomyopathy: mediated via endoplasmic reticulum stress and eggerated by norepinephrine. Mao W, S fukuoka, C Iwai, J Liu, VK Sharma, S-S Sheu, M Fu, and C-s Liang. Am J Heart Circ Physiol 293:H1636-H1645 (2007). Imgenex antibodies cited:
1. ATF6 (IMG-273): WB (Fig 7), analysis of ATF6 in nuclear fraction of rabbit left ventricle myocardium tissue lysates,  Authors describe cleaved forms of p90ATF6 in the nucleus: the cleaved forms are described as p60ATF6 and p36ATF6.
2. GAPDH (IMG-5019A): WB (Fig 4), GAPDH antibody used as a loading control in rabbit left ventricle myocardium tissue lysates.    
17. Carbon monoxide induces heme oxygenase-1 via activation of protein kinase R-like endoplasmic reticulum kinase and inhibits endothelial cell apoptosis triggered by endoplasmic reticulum stress. Kim KM, H-O Pae, M Zhung, R Park, Y-M Kim, H-T Chung. Circulation Research DOI: 10.1161/CIRCRESAHA.107.154781. (2007). WB (Figs 3, 4, 6): HUVEC (human umbilical vein endothelial cells),  p90ATF6 and cleaved p50ATF6 forms of ATF6 are detected.
18. The kinase inhibitor sorafenib induces cell death through a process involving induction of endoplasmic reticulum stress. Rahmani M, EM Davis, TR Crabtee, JR Habibi, TK Nguyen, P Dent and S Grant. Molecular and Cellular Biol. 27:5499-5513 (2007). WB: Fig 3A, U937 human leukemia cells treated with sorafenib.  Sorafenib is a multikinase inhibitor that induces apoptosis in human leukemia and other malignant cells. The authors show a decline in ATF6 (90 kDa band) expression in sorafenib-treated cells.   
19. Effects of triglyceride on ER stress and insulin resistance. Kim D-S, S-K Jeong, H-R Kim, D-S kim, S-W Chae, and H-J Chae. Biochem. Biophys. Res. Comm. doi:10.1016/j.bbrc.2007.08.151 (2007). WB (Fig 2), HepG2 cells treated with triglyceride. There was an increase of cleaved ATF6 over time with the triglyceride treatment.
20. GM1-Ganglioside-mediated activation of the unfolded protein response causes neuronal death in a neurodegenerative gangliosidosis. Tessitore A, MDP Martin, R Sano, Y Ma, L Mann,, A Ingrassia, ED Laywell, DA Steindler, LM Hendershot, and A d'Azzo. Molecular Cell 15:753-766 (2004). WB: Fig 7A, mice spinal cord tissue.  Lysosomal B-galactosidase -/- mice had increased levels of the 50 kDa cleaved form of ATF6 compared to wild-type mice.
21. Endoplasmic retiuclum stress contributes of beta cell apoptosis in type 2 diabetes.  Laybutt DR, AM Preston, MC Akerfeldt, JG Kench, AK Busch, AV Biankin, and TJ Biden. Diabetologia  50:752-763.  WB (Fig 3a and c), MIN6 mouse cells treated with DDIT3 (DNA-damage inducible transcript 3). MIN6 is a pancreatic beta cell line that retains glucose-inducible insulin secretion. The results showed an increase in the cleaved 50 kDa form of ATF6 at certain time points in DDIT3-treated compared to  BSA-treated control cells.  
22. Dynamic recruitment of transcription factors and epigenetic changes on the ER stress response gene promoters. Donati G, C Imbriano, and R Mantovani. Nucleic Acids Research 34:3116-3127 (2006). ChIP (Fig 5), HepG2 cells treated with thapsigargin.  
23. Effect on tumor cells of blocking survival response to glucose deprivation. Park H-R, A Tomida, S Sato, Y Tsukumo, J Yun, T Yamori, Y Hayakawa, T Tsuruo, K Shin-ya. J National Cancer Institute 96:1300-1310 (2004). WB  (HT1080 human fibrosarcoma cells):
Fig 2a. HT1080 cells transfected with full-length ATF6(F) or active ATF6(A) and treated with 2-deoxyglucose (2DG) or tunicamycin (TM) in the presence or absence of versipelostatin (VST).  ATF(F), un/under-glycosylated ATF6, intermediate ATF6 and ATF6 (A) forms are detected. 
Fig 2d. HT1080 cells transfected with ATF6 (A) and treated with 2DG in the presence or absence of VST. ATF6 (A) is shown, VST did not inhibit the production of ATF6 (A).
Fig 4e. ATF6 (F) and mock-transfected HT1080 cells.  ATF6(F) is shown; ATF6-transfected cells had a higher expression level of ATF6 (F) than the exogenous level seen in mock-tranfected cells.  Furthermore, the level of ATF6 (F) increased with increasing amounts (1 to 100 ng) of the ATF6 (F) plasmid used for transfection. 

ATF6 Transfection Validated: The ATF6 (IMG-273) antibody is validated by transfection to recognize ATF6 (F), un/under-glycosylated ATF6, intermediate ATF6 and ATF6 (A) forms in this citation (Figs 2a. 2d and 4e).

24. Regulation of ERGIC-53 gene transcription in response to endoplasmic reticulum stress. Renna M, MG Caporasco, S Bonatti, RJ Kaufman, and P Remondelli. JBC 282:22499-22512 (2007). ChIP: Fig 6B, Steady-state and thapsigargin (TG)-treated HeLa cells.  BiP/Grp78 and ERGIC-53 promoter regions were used as PCR primers in the ChIP assays to assess DNA ATF6 protein interactions. In TG-treated cells there was endogenous ATF6 binding on both the promoter regions.
25. Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cells. Davenport EL, HE Moore, AS Dunlop, SY Sharp, P Workman, GJ Morgan and FE DAvies. Blood 100:2641-2649 (2007). WB ([analysis of cleaved ATF6 nuclear fractions of human myeloma cells (U266, H929, MMI] treated with tunicamycin, thapsigargin, HSP inhibitors, or bortezomib): Figs 1C, 2C,and 3C. Results show increase of cleaved ATF6 under certain treatment conditions.
26. Bax inhibitor-1 regulates endoplasmic reticulum stress-associated reactive oxygen species and heme oxygenase-1 expression. Lee G-H, H-K Kim, S-W Chae, D-S Kim, K-C Ha, M Cuddy, C Kress, JC Reed, H-R Kim, and J-J Chae. JBC 282:21618-21628 (2007). WB: Neo and BI-1 transfected human HT1080 fibrosarcoma cells treated with thapsigargin or tunicamycin [(analysis of uncleaved ATF6 (p90)], Fig. 3A-C.   The results showed that the level of uncleaved ATF6 (p90) was lower in Neo than in BI-1 cells.  They also that the basal level of ATF6 (p90) decreased in Neo cells under ER stress but remained unchanged in the BI-1 cells under ER stress.
27. Nitric oxide induces coupling of mitochondrial signalling with the endoplasmic reticulum stress response. Weiming X, L Liu, IG Charles, and S Moncada. Nature Cell Biology 6:1129-1134 (2004).  WB (analysis of p90 and p50 ATF6):  Tex293 and EcR293 cells treated with various agents, Figs 1d, 2a, and 3b. Collectively the results show an increase of p50 ATF6 under certain treatment conditions.  
28. Long QT syndrome-associated I593R mutation in HERG postassium channel activates ER stress pathways. Keller SH, O Platoshyn, and J X-J Yuan. Cell Biochemistry and Biophysics 43:365-377. WB (analysis of full-length and active ATF6) and IP: HEK-293 and HeLa cells transfected with WT/WT HERG, WT/1593 HERG or 1593/1593 HERG,
Fig 6B: WB with ATF6, showing increase  of active (50 kDa ATF6) in WT/1593 and 1593/1593 HERG compared to WT/WT cells)
Fig 6C: IP with ATF6 and WB with Grp78, showing increase of Grp78 in WT/1593 and 1593/1593 HERG compared to WT/WT cells; IP/WB with ATF6 (similar results, data described but not shown)
29. ER and oxidative stresses are common mediators of apoptosis in both neurodegenderative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones.  Wei H, S Kim, Z Zhang, P Tsai K Wisniewski, A Mukherjee.  Human Molelular Genetics 17: 469-477 (2008). WB (human LSD (lysosomal storage disease) and normal cell lines), Figs. 1A,C; 3A,B,C.
30. Shiga toxin 1 induces apoptosis through the endoplasmic reticulum stress response in human monocytic cells. Lee S, M Lee, R Cherla, V Tesh. Cellular Microbiology 10:770-780 (2008). WB (human myelogenous leukemia cell line THP-1 cells), Fig. 1A.
Note: The  degradation of the 90 kDa ATF6 band was detected in THP-1 cells treated with Stx1. As shown in Fig 1A the levels of immunoreactive 90 kDa ATF6 were decreased beginning 2 h after Stx1 treatment and remained decreased over the time-course of the experiment. The Stx1 mutant failed to initiate the degradation of 90 kDa ATF6. The degradation of the 90 kDa band is considered to be an indication of ATF6 activation.
31. Eif-2a protects brainstem motoneurons in a murine model of sleep apnea. Zhu Y, P Fenik, G Zhan, B Sanfillipo-Cohn, N Naidoo, and SC Veasey. J Neuroscience 28:2168-2178. Mouse brain: IHC (frozen), Fig 2B; WB, Fig 1B. See Table I for information on antibody concentrations used. Immunofluorescence was used as a detection method for the IHC (frozen) images.
32. HMG-CoA reductase inhibitors activate the unfolded protein response and induce cytoprotective GRP78 expression. J Chen, M Wu, K Huang, W Lin. Cardiovascular Research 80: 138-150 (2008). WB (mouse RAW 264.7 cells), Fig. 5C.
33. cAbl kinase inhibitors overcome CD40-mediated drug resistance in CLL; Implications for therapeutic targeting of chemoresistant niches. Blood doi:10.1182/blood-2008-03-146704 (2008). WB (human chronic lympocytic leukemia cells), Supplementary Fig. 1a,b.
34. Chemical biology investigation of cell death pathways activated by endoplasmic reticulum stress reveals cytoprotective modulators of ASK1. Kim I, C Shu, W Xu, C Shiau, D Grant, S Vasile, N Cosford, J Reed. J Biol. Chem 283: 1593-1603 (2009).  WB (human CSM14.1 cells), Fig. 3.
35. ATF6a induces XBP1-independent expansion of endoplasmic reticulum. Bommiasamy H, SH Back, P Fagone, K Lee, S Meshinchi, E Vink, R Sruburi, M Frank, S Jackowski, RJ Kaufman, and JW Brewer. J Cell Sci 122:1626-1636 (2009). WB: ATF6 transfected CHO cells (Fig 2). The antibody detected ATF6a but not ATF6b transfected cells, thereby showing that the antibody specifically recognized the ATF6a isoform. Note: The antibody was transfected ATF6a validated by WB in Fig 2.

36. The unfolded protein response modulates toxicity of the expanded glutamine androgen receptor. Monzy Thomas, Zhigang Yu, Nahid Dadgar, Sooryanarayana Varambally, Jianjun Yu, Arul M. Chinnaiyan, and Andrew P. Lieberman. J. Biol. Chem., 280: 21264-21271 (2005). IMGENEX antibodies cited: ATF6 (IMG-273) [IF/ICC, Fig 2A (Quantification of nuclear active ATF6) ].  
37. Endoplasmic reticulum stress triggers an acute proteasome-dependent degradation of ATF6. Hong M, L Mingqing, C Mao, and AS Lee. J Cellular Biochemistry 92:723-732 (2004).  WB;
(1) NIH3T3 cells:
Fig 1C: Thapsigargin (Tg) teatment. At 0 hr, p90ATF6 was present at a low basal level. Treatment resulted in the transient diasppearance of p90ATF6 at 2 hr. By  8 hrs of treatment, ATF6 was elevated.
Fig 1D: Tunicamycin teatment At 0 hr, p90ATF6 was present at a low basal level. Treatment resulted in the diasppearance of p90ATF6. At 8 hr a faster-migrating ATF6 band appeared, referred to as the non-glycosylated form of ATF6.
Fig 3A: TG teatement and pretreatment with either ALLN, MG115 or z-DEVD-FMK.  Pretreatment with ALLN or MG115 partially rescued Tg-induced ATF6 degradation at 2 hr. z-DEVD-FMK did not prevent ATF6 degradation at 2 hr.
Fig 3B: Treated with calpastatatin peptide CI , Tg or peptide + Tg.  Treatment with the peptide did not prevent ATF6 degradation at 2 hr. + Tg or Tg alone
NIH3T3 This was transient and by 8 hr of Tg treatment, ATF6 was elevated.
Treatment diminished the level of p90ATF6.
Figs 4A and 4B: Treated with with combinantions Tg, MG115, and ALLN. Treatment with MG115, but not ALLN resulted in a slight increase in the steady state level of p90ATF6. 

2 (CHO cells):
Figs 2A-D: Various CHO constructs treated with Tg. Collectively the results show that both endogenous and ectopic p90ATF6 were subjected to acute proteolysis immediately following Tg stress.

IP/WB (NIT3T3 cells)
Fig 3C : Treated with TG in the presence of MG132, IP with ATF6 antibody, WB with Ubiquitin antibody (top) or IP/WB with ATF6 antibody. Results show that in non-stressed cells, ubiquitinated p90ATF6 was present and and that ubiquitination increased substantially within 1-2 h of Tg treatment.  Thus in non-stressed cells, p90ATF6 is subjected to constitutive proteasome-ubiquitin degradation.
38. Intrinsic capacities of molecular sensors of the unfolded protein response to sense alternate forms of endoplasmic reticulum stress. DuRose JB, AB Tam and M Niwa. Mol Biol Cell, 17:3095-3017 (2006). IMGENEX antibodies cited: 1.  ATF6 (IMG-273)  [WB, Fig 1: full-length and cleaved ATF6 in CHO cells) ], [WB, Fig 2 (full-length ATF6 in HeLa cells) ].