Disease relevance of Stfa1

• Given the roles of cathepsins in Ag processing and presentation, Stfa1 and Stfa2 alleles have the potential to control susceptibility to autoimmune disease at the level of both CD4(+)CD25(+) suppressor and CD4(+)CD25(-) effector T cells [1].
• Recent genetic studies identified structural polymorphisms in Stfa1 and Stfa2 as candidates for Aod1b, a locus controlling susceptibility to day three thymectomy (D3Tx)-induced autoimmune ovarian disease (AOD) [2].
• Increases in stefin expression are also apparent in me and mev skin and appear to reflect focal hyperplasia of stefin-producing epidermal cells as well as infiltration by stefin-expressing monocytic and granulocytic cells [3].
• The concentration of stefin A in tumor tissue in Lewis lung carcinoma was higher than in LS lymphosarcoma and HA-1-hepatoma ascitic cells, which can be explained by the degree of their malignancy [4].

High impact information on Stfa1

• Increased expression of the stefin A cysteine proteinase inhibitor occurs in the myelomonocytic cell-infiltrated tissues of autoimmune motheaten mice [3].
• These mutant mice have been previously shown to manifest abnormally high expression in the bone marrow of cDNAs encoding three members of the stefin family of cysteine proteinase inhibitors [3].
• Stfa1 and Stfa2 both act as fast and tight binding inhibitors of endopeptidases papain and cathepsins L and S, however their interaction with exopeptidases cathepsins B, C and H was several orders of magnitude weaker compared to human, porcine and bovine Stfa [2].
• Stefin A (Stfa) acts as a competitive inhibitor of intracellular papain-like cysteine proteases which play important roles in normal cellular functions such as general protein turnover, antigen processing and ovarian follicular growth and maturation [2].
• A number of genes associated with differentiation and development were also physically clustered on mouse chromosome 16, including 16B3 that contains several Stefins and stefin-like genes, and 16A1 containing a number of keratin associated protein genes [5].

Biological context of Stfa1

• Analysis of interspecific backcross mice indicates that the genes encoding the three mouse stefins all map to mouse chromosome 16, a localization that is consistent with the recent assignment of the human stefin A gene to a region of conserved homology between human chromosome 3q and the proximal region of mouse chromosome 16 [6].
• The open reading frames of the stefin cDNAs encode proteins of approximately 11.5 kDa that show between 50 and 92% identity to sequences of stefins isolated from various other species [6].
• Data from Southern analysis suggest that the murine stefin gene family encompasses at least 6 and possibly 10-20 members, all of which appear to be clustered in the genome [6].

Anatomical context of Stfa1

• In contrast, the 14 kDa and 70 kDa bands both crossreacted with a polyclonal antibody to stefin A, suggesting that the cysteine protease inhibitor associated with Hepa cl 9 membranes may be a modified form of stefin A [7].
• Cystatin C was found on the top surfaces of both cell lines, whereas stefin A was found only on the top surface of the embryonic liver cells [8].

Other interactions of Stfa1

• Antibodies raised against E 8 reacted with stefin but not with kininogen or cystatin [9].
• The concentration of stefin A (cystatin A in mice) was measured in animals with experimental tumors (LS lymphosarcoma, HA-1-hepatoma, and Lewis lung carcinoma) during effective antitumor therapy [4].

Analytical, diagnostic and therapeutic context of Stfa1

• We report here on the molecular cloning and chromosomal localization of three newly identified members of the murine stefin gene family [6].

References