Reactome | PERK regulates gene expression

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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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