Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress.
Under conditions of endoplasmic reticulum (ER) stress, mammalian cells induce both translational repression and the unfolded protein response that transcriptionally activates genes encoding ER-resident molecular chaperones. To date, the only known pathway for translational repression in response to ER stress has been the phosphorylation of eIF-2alpha by the double-stranded RNA-activated protein kinase (PKR) or the transmembrane PKR-like ER kinase (PERK). Here we report another pathway in which the ER transmembrane kinase/ribonuclease IRE1beta induces translational repression through 28S ribosomal RNA cleavage in response to ER stress. The evidence suggests that both pathways are important for efficient translational repression during the ER stress response.
Iwawaki
T
T
Research and Education Center for Genetic Information, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0101, Japan.
Hosoda
A
A
Okuda
T
T
Kamigori
Y
Y
Nomura-Furuwatari
C
C
Kimata
Y
Y
Tsuru
A
A
Kohno
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004318:Doxycycline / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004722:Endoribonucleases; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012339:RNA, Ribosomal, 28S / Q000378:metabolism; D016415:Sequence Alignment; D014162:Transfection; D014415:Tunicamycin / Q000494:pharmacology; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004318:Doxycycline; D004722:Endoribonucleases; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D012339:RNA, Ribosomal, 28S; D014415:Tunicamycin; D019892:eIF-2 Kinase; C403982:ERN2 protein, human