Disease relevance of HHAT

• Although transforming activity was not detected in the NIH-3T3 assay, MART-2 with the mutation in the P-loop may be involved in the generation of melanoma through a loss of GTP binding activity [1].
• By screening 36 various cancer cell lines using single-strand conformation polymorphism, a possible mutation in the P-loop of MART-2 was found in one squamous cell lung cancer cell line, EBC1 [1].
• Resistance to (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU), an experimental anticancer compound, was investigated in the chloroethylnitrosourea-sensitive Mer- SK-MG-1 and -resistant Mer- SKI-1 human glioma cell lines [2].
• Comparison of SKI-1 cleavage efficiency between peptides representing Lassa virus GP2 and CCHF virus Gn cleavage sites suggests that amino acids flanking the RRLL may modulate the efficiency [3].
• Crimean-Congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase SKI-1 [3].

High impact information on HHAT

• However, part of the chloroethylnitrosourea resistance in SKI-1 cells is not secondary to decreased accumulation [2].
• The 2-fold resistance at 22 degrees C was similar to that of 1,3-bis(2-chloroethyl)-1-nitrosourea at 37 and 22 degrees C. These findings indicate that increased cytotoxicity in SK-MG-1 cells is associated with a greater accumulation of SarCNU via an epinephrine-sensitive carrier that is not detectable in SKI-1 cells [2].
• Isolation of a new melanoma antigen, MART-2, containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes [1].
• Transfection of NIH-3T3 with the mutated MART-2 did not result in the development of significant foci [1].
• Using cDNA expression cloning, a cDNA encoding a novel human melanoma Ag, MART-2 (melanoma Ag recognized by T cells-2), recognized by HLA-A1-restricted CD8(+) T cells from tumor-infiltrating lymphocytes (TIL1362) was isolated from an autologous melanoma cell line, 1362 mel [1].

Biological context of HHAT

• Altered cytotoxicity of (2-chloroethyl)-3-sarcosinamide-1-nitrosourea in human glioma cell lines SK-MG-1 and SKI-1 correlates with differential transport kinetics [2].
• In an effort to enhance the selectivity and potency of SKI-1 inhibition, a hexapeptidyl derivative containing SKI-1 consensus sequence, Ac-Val-Phe-Arg-Ser-Leu-Lys-AEBSF, was prepared [4].

Anatomical context of HHAT

• The T cell epitope for TIL1362, FLEGNEVGKTY, was identified to be encoded by the mutated sequence of the MART-2 Ag [1].
• These in vitro findings were confirmed by expression of wild-type or mutant CCHF virus glycoproteins in CHO cells engineered to express functional or nonfunctional SKI-1 [3].

Associations of HHAT with chemical compounds

• Human site-1-protease (S1P, MEROPS S08.8063), also widely known as subtilisin/kexin isozyme 1 (SKI-1), is a membrane bound subtilisin-related serine protease, that belongs to a group of nine mammalian proprotein convertases [5].

Analytical, diagnostic and therapeutic context of HHAT

• Since the prosomatostatin sequence R8-Q9-F10-L11 \ qualifies as a potential SKI-1 substrate, using a vaccinia virus expression system along with HPLC and radioimmunoassays, we observed that overexpression of recombinant SKI-1 in COS-1 and HEK-293 cells significantly increased the production of PSST[1-10] [6].

References