Gamma-secretase subunit PEN-2

Definition:

Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity.

References:

[1]. Dieter Edbauer, et al. Reconstitution of gamma-secretase activity. Nat Cell Biol. 2003 May;5(5):486-8. [Content Brief]

[2]. Guanghui Yang, et al. Structural basis of Notch recognition by human γ-secretase. Nature. 2019 Jan;565(7738):192-197. [Content Brief]

[3]. Rui Zhou, et al. Recognition of the amyloid precursor protein by human γ-secretase. Science. 2019 Feb 15;363(6428):eaaw0930. [Content Brief]

[4]. Wen-jie Luo, et al. PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. J Biol Chem. 2003 Mar 7;278(10):7850-4. [Content Brief]

[5]. Laura Marlow, et al. APH1, PEN2, and Nicastrin increase Abeta levels and gamma-secretase activity. Biochem Biophys Res Commun. 2003 Jun 6;305(3):502-9. [Content Brief]

[6]. W Taylor Kimberly, et al. Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6382-7. [Content Brief]

[7]. Oliver Holmes, et al. Pen-2 is essential for γ-secretase complex stability and trafficking but partially dispensable for endoproteolysis. Biochemistry. 2014 Jul 15;53(27):4393-406. [Content Brief]

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