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PERK regulates gene expression
Stable Identifier
R-HSA-381042
Type
Pathway
Species
Homo sapiens
Compartment
cytosol
,
endoplasmic reticulum lumen
,
endoplasmic reticulum membrane
,
nucleoplasm
ReviewStatus
5/5
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Cellular responses to stimuli (Homo sapiens)
Cellular responses to stress (Homo sapiens)
Unfolded Protein Response (UPR) (Homo sapiens)
PERK regulates gene expression (Homo sapiens)
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PERK (EIF2AK3) 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.
Literature References
PubMed ID
Title
Journal
Year
17956313
PERK in the life and death of the pancreatic beta-cell
Herbert, TP
Biochem Soc Trans
2007
18048764
The role for endoplasmic reticulum stress in diabetes mellitus
Cardozo, AK
,
Eizirik, DL
,
Cnop, M
Endocr Rev
2008
18038217
Endoplasmic reticulum stress responses
Schröder, M
Cell Mol Life Sci
2008
18436705
The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes
Kaufman, RJ
,
Scheuner, D
Endocr Rev
2008
Participants
Events
Dissociation of PERK:BiP Heterodimer
(Homo sapiens)
Dimerization of PERK
(Homo sapiens)
EIF2AK3 (PERK) phosphorylates EIF2S1 (eIF2-alpha)Phosphorylation of eIF2-alpha by PERK
(Homo sapiens)
Translation of ATF4
(Homo sapiens)
ATF4 activates genes in response to endoplasmic reticulum stress
(Homo sapiens)
Participates
as an event of
Unfolded Protein Response (UPR) (Homo sapiens)
Event Information
Go Biological Process
PERK-mediated unfolded protein response (0036499)
Orthologous Events
PERK regulates gene expression (Bos taurus)
PERK regulates gene expression (Caenorhabditis elegans)
PERK regulates gene expression (Canis familiaris)
PERK regulates gene expression (Drosophila melanogaster)
PERK regulates gene expression (Gallus gallus)
PERK regulates gene expression (Mus musculus)
PERK regulates gene expression (Rattus norvegicus)
PERK regulates gene expression (Sus scrofa)
PERK regulates gene expression (Xenopus tropicalis)
Authored
May, B (2009-06-02)
Reviewed
Gillespie, ME (2008-12-02)
D'Eustachio, P (2008-12-02)
Matthews, L (2008-12-02)
Urano, F (2010-04-30)
Created
May, B (2008-11-19)
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