Arabidopsis bZIP60 Is a Proteolysis-Activated Transcription Factor Involved in the Endoplasmic Reticulum Stress Response

Abstract

Proteins synthesized in the endoplasmic reticulum (ER) of eukaryotic cells must be folded correctly before translocation out of the ER. Disruption of protein folding results in the induction of genes for ER-resident chaperones, for example, BiP. This phenomenon is known as the ER stress response. We report here that bZIP60, an Arabidopsis thaliana basic leucine zipper (bZIP) transcription factor with a transmembrane domain, is involved in the ER stress response. When compared with wildtype Arabidopsis plants, homozygous bzip60 mutant plants show a markedly weaker induction of many ER stressresponsive genes. The bZIP60 protein resides in the ER membrane under unstressed condition and is cleaved in response to ER stress caused by either tunicamycin or DTT. The N-terminal fragment containing the bZIP domain is then translocated into the nucleus. Cleavage of bZIP60 is independent of the function of Arabidopsis homologs of mammalian S1P and S2P proteases, which mediate the proteolytic cleavage of the mammalian transcription factor ATF6. In Arabidopsis, expression of the bZIP60 gene and cleavage of the bZIP60 protein are observed in anthers in the absence of stress treatment, suggesting that the ER stress response functions in the normal development of active secretory cells.

Manufacturing antibodies in the plant cell

“…Deleted: [44,45] Deleted: a Deleted: also Deleted: [46] Page 12 of 38 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Once the link between UPR and SAR is established, it is interesting to look for plant regulators of UPR as potential candidates for activating the secretory pathway in plants.…”

“…In Arabidopsis, at least two bZIP transcription factors, bZIP60 and bZIP28, were found to regulate ER-stress [45]. Interestingly, bZIP60 is translocated to the nucleus in a truncated form, similar to the activation mechanism of mammalian ATF6 [46]. In agreement with a model that unifies ER-stress response and developmentally activated secretion, the cleaved form of bZIP60 was seen to accumulate in anther tapetal cells, which are known to secrete large amounts of proteins and lipids and whose ER is hypertrophied, as observed in ultrastructural analysis.…”

The physiological role of the unfolded protein response in plants

“…Furthermore, transactivation assays were used to show that, like AtbZIP60, NtbZIP60 needs to be processed in order to function as an active transcription factor in vivo. Iwata et al (2008) recently suggested that AtbZIP60 is processed under ER stress conditions, since a polyclonal antibody against AtbZIP60 revealed two proteins when cells in culture were treated with tunicamycin or DTT. The analysis showed that the smaller protein corresponded to the cleaved form of AtbZIP60.…”

Bax inhibitor-1: a highly conserved endoplasmic reticulum-resident cell death suppressor

“…39 In the Arabidopsis root, alterations in AtBI-1 levels do not appear to significantly influence the expression levels of some of the key ER stress responsible genes, suggesting that AtBI-1 functions in parallel to this transcriptional upregulation. 37 However, it would be interesting if plant BI-1 function is associated with active transcriptional control in ER stress response through direct interaction with plant orthologue of IRE1 40 or other cryptic factors that may control ER stress-responsive genes in plants.…”

“…35 Expression of AtBI-1 can be induced transcriptionally through activation of the ER-resident bZIP transcription factors AtZIP60. 37 This up-regulation of BI-1 should increase the amount of BI-1 on the ER membrane and support its activity as a survival factor involved in an anti-PCD pathway. However, AtBI-1 appears to act in parallel to the unfolded protein response (UPR) that is induced during ER-stress and is not involved in the signaling of the UPR per se, as alterations in AtBI-1 levels did not significantly impact expression of UPR marker genes.…”