Reactome: A Curated Pathway Database
Attention
The EBI data centre will be shutting down from the afternoon (BST) of Friday 26th August until the afternoon of Tuesday 30th August 2016 for essential maintenance. This might have an impact on some Reactome services and we apologize for any inconvenience.

PERK regulates gene expression

Stable Identifier
R-HSA-381042
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
Participants
Participant Of
Orthologous Events