Disease relevance of RCE1

• On the physiological importance of endoproteolysis of CAAX proteins: heart-specific RCE1 knockout mice develop a lethal cardiomyopathy [1].
• Fluorescence in situ hybridization experiments showed that the human FACE-1 gene maps to 1p34, whereas FACE-2 is located at 11q13, a region frequently amplified in human carcinomas and lymphomas [2].
• A 32-year-old male patient developed headaches, vomiting, blurring of vision, and focal seizures of the left side of the face 2 months after a renal transplant [3].
• A 4-year-old boy with cystic fibrosis developed hypertension, rapid weight gain and a moon face 2 weeks after starting a combined treatment of oral itraconazole and inhaled budesonide for a suspected allergic bronchopulmonary aspergillosis [4].

High impact information on RCE1

• A carboxyl-terminal interaction of lamin B1 is dependent on the CAAX endoprotease Rce1 and carboxymethylation [5].
• After farnesylation, the 3 amino acids downstream from the farnesyl cysteine (the -aaX of the CaaX motif) are released by RAS-converting enzyme 1 (RCE1) [6].
• Ras and Rho proteins possess a C-terminal CAAX motif (C is cysteine, A is usually an aliphatic residue, and X is any amino acid), in which the cysteine is prenylated, followed by proteolytic cleavage of the AAX peptide and carboxyl methylation by the Rce1 CAAX protease and Icmt methyltransferase, respectively [7].
• Rab38(CAKS) is not methylated in vivo, presumably because of the inhibitory action of the lysine residue within the AAX motif for cleavage by Rce1 [7].
• Removal of the three C-terminal amino acids of farnesylated K-Ras with the specific endoprotease Rce1p abolished its binding to microtubules [8].

Biological context of RCE1

• Following prenylation, these proteins usually undergo endoproteolytic processing by the RCE1 protease and then carboxyl methylation by a unique methyltransferase known as isoprenylcysteine carboxyl methyltransferase (ICMT) [9].
• In this study, a portion of a putative human homologue of RCE1 (hRCE1) was identified in a human expressed sequence tag data base, and the corresponding cDNA was cloned [10].
• A human gene responsible for one of the steps in Ras post-translational modification and membrane localization, hRCE1, encodes a 35-kDa membrane-associated endoprotease [11].
• Cloned RCE1 units were used for fluorescent in situ hybridization (FISH) analysis, and signals were observed on almost every primary constriction of rice chromosomes [12].
• The lambda RCB11 clone contained at least four A/T-rich regions, which are candidate for matrix attachment regions (MARs), in the sequences between the RCE1 repeats [12].

Anatomical context of RCE1

• RCE1 Corneal Epithelial Cell Line: Its Variability on Phenotype Expression and Differential Response to Growth Factors [13].
• Membranes for biohybrid organs such as the biohybrid liver support system have to face 2 different environments, namely blood and tissue cells [14].

Associations of RCE1 with chemical compounds

• We examined hRCE1 activity using farnesylated 9 aa peptides with the core sequence, KSKTKC(farnesyl)VIM [(farnesyl) = (f)], from the C-terminus of K-Ras [11].
• Thus, hRCE1 has important functional interaction with the P2' and P3' substrate positions in addition to the farnesylated cysteine at the scissile bond site [15].

Other interactions of RCE1

• On the basis of these results, we suggest that inhibition of Face-1 and/or Face-2 could be part of strategies directed to block the functioning of prenylated proteins activated in oncogenic processes, including Ras proteins [2].
• Recombinant hRCE1 so produced recognized both farnesylated and geranylgeranylated proteins as substrates, including farnesyl-Ki-Ras, farnesyl-N-Ras, farnesyl-Ha-Ras, and the farnesylated heterotrimeric G protein Ggamma1 subunit, as well as geranylgeranyl-Ki-Ras and geranylgeranyl-Rap1b [10].
• Human ras-converting enzyme (hRCE1) endoproteolytic activity on K-ras-derived peptides [11].
• We also found that hRCE1 cleaved modified versions of KSKTKC(f)VIM that incorporated either MCA or ABZ fluorescent chromophores at the N-terminus, and quenching-group-containing amino acids at the V or M, but not the I, amino acid positions of VIM [11].
• We conclude that EGF and TGF-alpha are the major effectors of RCE1 cell proliferation [13].

Analytical, diagnostic and therapeutic context of RCE1

• Cleavage of KSKTKC(f)VIM and modified versions of this peptide by hRCE1 was initially evaluated by HPLC product resolution and quantitation [11].

References