Cleavage of the membrane-bound transcription factor OASIS in response to endoplasmic reticulum stress.
When unfolded or misfolded proteins accumulate in the endoplasmic reticulum (ER), unfolded protein response (UPR) signals are transmitted from the ER to the nucleus and cytoplasm to facilitate protein folding. OASIS (old astrocyte specifically induced substance) is an ER stress transducer in astrocytes, a membrane-bound transcription factor that activates genes in the ER stress response. When unfolded proteins accumulate in the ER, OASIS is cleaved at the membrane to release its cytoplasmic domain, which then enters the nucleus and activates target genes. Here, we showed that OASIS is processed by Site-1 and -2 proteases (S1P and S2P), enzymes that reside at the Golgi apparatus and process activating transcription factor 6 (ATF6), in response to ER stress. We also showed that the cleavage of OASIS is triggered by its translocation to the Golgi apparatus. All deletion mutants for luminal domain of OASIS showed that proteolytic processing and translocation to the Golgi apparatus remained intact, indicating that OASIS does not have significant sequences for Golgi localization signals, different from the case of ATF6, and that there could be other systems for translocation of OASIS to the Golgi apparatus in response to ER stress.
Murakami
Tomohiko
T
Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.
Kondo
Shinichi
S
Ogata
Maiko
M
Kanemoto
Soshi
S
Saito
Atsushi
A
Wanaka
Akio
A
Imaizumi
Kazunori
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000502:physiology*; D017930:Genes, Reporter; D005910:Glioma; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D013314:Stress, Mechanical; D014162:Transfection
C119923:Creb3l1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D009419:Nerve Tissue Proteins