Cathepsin E (EC 3.4.23.34) — a review

Abstract

Cathepsin E belongs to the third class of enzymes -hydrolases, a subclass of peptide bond hydrolases and a sub-subclass of endopeptidases with aspartic catalytic sites. Cathepsin E is an endopeptidase with substrate specificity similar to that of cathepsin D. In a human organism, cathepsin E occurs in: erythrocytes, thymus, dendritic cells, epithelial M cells, microglia cells, Langerhans cells, lymphocytes, epithelium of gastrointestinal tract, urinary bladder, lungs, osteoclasts, spleen and lymphatic nodes. In human cells, loci of the gene of pre-procathepsin E are located on chromosome 1 in the region 1231-32. The catalytic site of cathepsin E is two residues of aspartic acid -Asp96 and Asn281, occurring in amino acid triads with sequences DTG96-98 and DTG281-283. To date, no particular role of cathepsin E in the metabolism of proteins in normal tissues has been found. However, it is known that there are many documented pathological conditions in which overexpression of cathepsin E occurs.

Nkx2-1 Represses a Latent Gastric Differentiation Program in Lung Adenocarcinoma

“…Hnf4α and Pdx1 are transcription factors that regulate gastrointestinal differentiation (Hayhurst et al, 2001; Offield et al, 1996). Cathepsin E (Ctse) and Gastrokine 1 (Gkn1, a stomach-specific protein), are secreted proteins (Chlabicz et al, 2011; Oien et al, 2004). These four proteins were undetectable in normal lung and Nkx2-1-positive control tumors, but were expressed Kras LA2 tumors 10 weeks after Nkx2-1 deletion (LA2ΔN) and in KN tumors.…”

Peptide-Modulated Activity Enhancement of Acidic Protease Cathepsin E at Neutral pH

“…Cathepsin E, which usually operates at acidic pH [10], has been shown to induce cancer cell apoptosis [11, 12] and inhibit tumor angiogenesis [13] at neutral pH, which promotes the finding of its activators for cancer therapy. Therefore, in this study, we sought to obtain peptides with sufficiently high biological activity that would be suitable for medical purposes.…”

Mass spectrometric characterization of limited proteolysis activity in human plasma samples under mild acidic conditions

“…In-vitro cleavages of HSA by cathepsin D have been published [10,69]. The experimental settings rather match with conditions used for high substrate turnover.…”

“…Setting the amino acid residues Val-Leu as P2 and P1 and Ile-Ala to P1 0 , P2 0 returned cathepsin E as the most likely protease to have done the cleavage. Yet, as cathepsin D also belongs to the same subclass of endopeptidases and possesses a substrate specificity that is very similar to that of cathepsin E [10], it should be considered as (the other) responsible protease as well.…”

“…As lysosomal or endosomal proteases have pH optima of approx. 5.5-6.5 [10], we intended to initiate the assumed proteolytic activity in plasma by dropping the pH to 6, despite the fact that the samples of interest should normally not have suffered from such severe injuries. An ideal measure for monitoring flap quality is studying plasma proteins from blood that passed through the transplanted tissue because plasma protein compositions reacts dynamically with respect to tissue condition changes.…”