RCE1 cleaves S-Farn proRAS proteins

Stable Identifier
R-HSA-9647999
Type
Reaction [transition]
Species
Homo sapiens
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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
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
12433685 Hematologic effects of inactivating the Ras processing enzyme Rce1

Aiyagari, AL, Taylor, BR, Aurora, V, Young, SG, Shannon, KM

Blood 2003
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
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Catalyst Activity
Title
cysteine-type endopeptidase activity of PolyUb-RCE1 [endoplasmic reticulum membrane]
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