PERK regulates gene expression

Stable Identifier
R-HSA-381042
Type
Pathway
Species
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
18048764 The role for endoplasmic reticulum stress in diabetes mellitus

Eizirik, DL, Cardozo, AK, Cnop, M

Endocr Rev 2008
17956313 PERK in the life and death of the pancreatic beta-cell

Herbert, TP

Biochem Soc Trans 2007
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

Scheuner, D, Kaufman, RJ

Endocr Rev 2008
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