Reactome | RCE1 cleaves S-Farn proRAS proteins

RCE1 cleaves S-Farn proRAS proteins

Stable Identifier

R-HSA-9647999

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane

ReviewStatus

5/5

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After prenylation, RAS proteins undergo C-terminal endoproteolysis by RAS-converting enzyme I (RCE1), which removes the aaX residues of the CaaX motif (Otto et al, 1999; Hollander et al, 2000; reviewed in Hampton et al, 2018; Ahearn et al, 2018). RCE1-mediated cleavage is required for RAS plasma membrane localization and function (Michaelson et al, 2005). RCE1 is ubiquitinated in its active form, and deubiquitination by USP17L2 abrogates its catalytic activity and inhibits signaling through the RAS-RAF MAP kinase pathway (Burrows et al, 2009). RCE1 has thus been investigated as a potential therapeutic target in RAS driven disease. Despite some promising studies, the effects of RCE1 inactivation appear unpredictable and can lead to unexpected activation of RAS signaling through mechanisms that are not fully understood (Bergo et al, 2002; Aiyagari et al, 2003; Kim et al, 1999; Chen et al, 1998; Chen et al, 1999; Wahlstrom et al, 2007).

Literature References

PubMed ID	Title	Journal	Year
12433685	Hematologic effects of inactivating the Ras processing enzyme Rce1 Aiyagari, AL, Taylor, BR, Aurora, V, Young, SG, Shannon, KM	Blood	2003
15659645	Postprenylation CAAX processing is required for proper localization of Ras but not Rho GTPases Michaelson, D, Ali, W, Chiu, VK, Bergo, M, Silletti, J, Wright, L, Young, SG, Philips, M	Mol. Biol. Cell	2005
10085068	Cloning and characterization of a mammalian prenyl protein-specific protease Otto, JC, Kim, E, Young, SG, Casey, PJ	J. Biol. Chem.	1999
11038283	Human ras-converting enzyme (hRCE1) endoproteolytic activity on K-ras-derived peptides Hollander, I, Frommer, E, Mallon, R	Anal. Biochem.	2000
10085069	Disruption of the mouse Rce1 gene results in defective Ras processing and mislocalization of Ras within cells Kim, E, Ambroziak, P, Otto, JC, Taylor, B, Ashby, M, Shannon, K, Casey, PJ, Young, SG	J. Biol. Chem.	1999
19188362	USP17 regulates Ras activation and cell proliferation by blocking RCE1 activity Burrows, JF, Kelvin, AA, McFarlane, C, Burden, RE, McGrattan, MJ, De la Vega, M, Govender, U, Quinn, DJ, Dib, K, Gadina, M, Scott, CJ, Johnston, JA	J. Biol. Chem.	2009
10667208	Selective inhibition of ras-transformed cell growth by a novel fatty acid-based chloromethyl ketone designed to target Ras endoprotease Chen, Y	Ann. N. Y. Acad. Sci.	1999
29311131	Posttranslational Modifications of RAS Proteins Ahearn, I, Zhou, M, Philips, MR	Cold Spring Harb Perspect Med	2018
9851253	Inhibition of K-ras-transformed rodent and human cancer cell growth via induction of apoptosis by irreversible inhibitors of Ras endoprotease Chen, Y	Cancer Lett.	1998
29424242	Rce1: mechanism and inhibition Hampton, SE, Dore, TM, Schmidt, WK	Crit. Rev. Biochem. Mol. Biol.	2018
11739732	Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation Bergo, MO, Ambroziak, P, Gregory, C, George, A, Otto, JC, Kim, E, Nagase, H, Casey, PJ, Balmain, A, Young, SG	Mol. Cell. Biol.	2002