N-glycosylation of ATF6beta is essential for its proteolytic cleavage and transcriptional repressor function to ATF6alpha.
Activating transcription factor 6 (ATF6), a member of the ATF/CREB family of transcription factors, has two isoforms of 90-kDa (p90ATF6alpha) and 110-kDa (p110 ATF6beta) as endoplasmic reticulum (ER) transmembrane glycoprotein. ATF6beta contains five evolutionarily conserved N-linked glycosylation sites and is a key transcriptional repressor of ATF6alpha, which contribute to regulating the strength and duration of ATF6-dependent ER stress response (ERSR) gene induction. Although it is well established that p110ATF6beta can be cleaved and generate a nuclear form of 60-kDa (p60ATF6beta) that inhibits ATF6alpha-mediated ERSR genes activation, the functional significance of p110 ATF6beta N-linked glycosylation is unknown. Herein, we found that the fully unglycosylated ATF6beta cannot be proteolytic cleaved, be detectable in nucleus after dithiothreitol treatment, and repress the transcriptional activity of ATF6alpha. These results provide the first evidence that unglycosylated ATF6beta may directly facilitate the expression of ERSR genes by losing its repressor function to ATF6alpha.
Guan
Dongyin
D
Department of Biochemistry, Shanghai Medical College, Fudan University, 130 Dong-An Road, Shanghai 200032, People's Republic of China.
Wang
Hao
H
Li
Veronica E
VE
Xu
Yingying
Y
Yang
Min
M
Shen
Zonghou
Z
D051702:Activating Transcription Factor 6 / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004229:Dithiothreitol / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D006023:Glycoproteins; D004229:Dithiothreitol