loading...| Preferred Name |
PERK regulated gene expression |
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| Synonyms |
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| Definitions |
Reviewed: D'Eustachio, P, Matthews, L, Gillespie, ME, 2008-12-02 16:25:31 Reviewed: Urano, F, 2010-04-30 Edited: May, B, Gopinathrao, G, 2008-11-19 19:22:37 Authored: May, B, 2009-06-02 00:51:49 PERK is a single-pass transmembrane protein located in the endoplasmic reticulum (ER) membrane such that the N-terminus of PERK is luminal and the C-terminus is cytosolic. PERK is maintained in an inactive form by interaction of its luminal domain with BiP, an ER chaperone. BiP also binds unfolded proteins and so BiP dissociates from PERK when unfolded proteins accumulate in the ER. Dissociated PERK monomers spontaneously form homodimers and the homodimeric form of PERK possesses kinase activity in its cytosolic C-terminal domain. The kinase specifically phosphorylates the translation factor eIF2alpha at Ser52, resulting in an arrest of translation. Thus translation of proteins targeted to the ER is downregulated. The translation arrest also causes depletion of Cyclin D1, a rapidly turned over protein. The depletion of Cyclin D1 in turn causes arrest of the cell cycle in G1 phase. |
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| ID |
http://purl.obolibrary.org/obo/HINO_0016044 |
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| comment |
Reviewed: D'Eustachio, P, Matthews, L, Gillespie, ME, 2008-12-02 16:25:31 Reviewed: Urano, F, 2010-04-30 Edited: May, B, Gopinathrao, G, 2008-11-19 19:22:37 Authored: May, B, 2009-06-02 00:51:49 PERK is a single-pass transmembrane protein located in the endoplasmic reticulum (ER) membrane such that the N-terminus of PERK is luminal and the C-terminus is cytosolic. PERK is maintained in an inactive form by interaction of its luminal domain with BiP, an ER chaperone. BiP also binds unfolded proteins and so BiP dissociates from PERK when unfolded proteins accumulate in the ER. Dissociated PERK monomers spontaneously form homodimers and the homodimeric form of PERK possesses kinase activity in its cytosolic C-terminal domain. The kinase specifically phosphorylates the translation factor eIF2alpha at Ser52, resulting in an arrest of translation. Thus translation of proteins targeted to the ER is downregulated. The translation arrest also causes depletion of Cyclin D1, a rapidly turned over protein. The depletion of Cyclin D1 in turn causes arrest of the cell cycle in G1 phase. |
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| definition source |
Pubmed18048764 Reactome, http://www.reactome.org Pubmed17956313 Pubmed18038217 Pubmed18436705 |
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| label |
PERK regulated gene expression |
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| prefixIRI |
HINO:0016044 |
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| prefLabel |
PERK regulated gene expression |
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| seeAlso |
ReactomeREACT_18277 GENE ONTOLOGYGO:0006987 Reactome Database ID Release 43381042 |
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| subClassOf | ||
| has_part |
http://purl.obolibrary.org/obo/HINO_0008871 http://purl.obolibrary.org/obo/HINO_0016047 http://purl.obolibrary.org/obo/HINO_0014626 |