Disease relevance of CSTL1

• CMAP: a novel cystatin-like gene involved in liver metastasis [1].
• Is the cystatin-like domain of TSL functionally active in external ocular infections and during the normal diurnal cycle [2]?

High impact information on CSTL1

• The "occluding loop' does not allow cystatin-like protein inhibitors to bind to cathepsin B as they do to papain, consistent with the reduced affinity of these protein inhibitors for cathepsin B compared with the related plant enzymes [3].
• Using the crystalline structure of cystatin to computer model domain-3, LDC27 and CNA13 were located in the second hairpin loop of the reactive site of cystatin-like proteins (Bode, W., Engh, R., Musil, D., Thiele, U. Huber, R., Karshikov, A., Brzin, J., Kos, J., and Turk, V. (1988) EMBO J. 7, 2593-2599) [4].
• However, preferential cleavage of T-kininogen close to the junction between cystatin-like domains released fragments which, provided they included cystatin-like domains 2 and/or 3, strongly inhibited papain and cathepsin L. The fragments were inhibitory even when parts of the amino-terminal ends of the domains were lacking [5].
• It is concluded that alpha 2-HS glycoprotein represents a structural prototype of a novel family among the cystatin superfamily, characterized by the presence of two cystatin-like building blocks [6].
• The proteinase-sensitive regions are located at the junctions of the three cystatin-like domains constituting the kininogen heavy chain [7].

Biological context of CSTL1

• Cystatins as calpain inhibitors: engineered chicken cystatin- and stefin B-kininogen domain 2 hybrids support a cystatin-like mode of interaction with the catalytic subunit of mu-calpain [8].
• Each of cystatin-like domains I and II of HRG is encoded by three exons, exons I to III and exons IV to VI, respectively, like those of other members of the cystatin superfamily [9].

Anatomical context of CSTL1

• Molecular cloning and characterization of a novel cystatin-like molecule, CLM, from human bone marrow stromal cells [10].
• T-kininogen, a cystatin-like molecule, inhibits ERK-dependent lymphocyte proliferation [11].
• Characterization of monoclonal antibodies to human salivary (glyco) proteins. Cellular localization of mucin, cystatin-like 14 kD protein and 20 kD glycoprotein in the human submandibular gland [12].
• Cystatin-like immunoreactive material was also demonstrated in human lacrimal gland using antibodies against human cystatin S [13].

Associations of CSTL1 with chemical compounds

• The presence of cystatin-like inhibitors in lower eukaryotes such as protozoan parasites has not yet been demonstrated, although these cells express large quantities of cysteine proteases and may also count on endogenous inhibitors to regulate cellular proteolysis [14].
• The high gene density of Fugu is shown by the close proximity of a cystatin-like gene 1503 bp from the dopamine receptor gene D222 [15].

Regulatory relationships of CSTL1

• Analyses of endogenous cathepsin B inhibitor activity in control and heat-treated cell homogenates after fractionation by fast protein liquid chromatography suggested that alterations in cystatin-like, cysteine protease inhibitor activities contribute to increased levels of cathepsin activities in metastatic MCF-7/AdrR cells [16].

Other interactions of CSTL1

• Three cystatin-like domains in the kininogen gene and the salivary cystatin genes share the same gene organizations [17].
• The highly conserved glycyl residue, thought to be involved in the inhibitory reactive site of cystatin-like inhibitors, was not required in purified domain 3 for inhibition of cathepsin L [5].
• Cathepsin F would therefore be the first cysteine protease zymogen containing a cystatin-like domain [18].
• The N-terminal part of recombinant human tear lipocalin/von Ebner's gland protein confers cysteine proteinase inhibition depending on the presence of the entire cystatin-like sequence motifs [19].
• The N-terminal fragment (295 amino acids), consisting of two cystatin-like modules, is bound to the proline-rich C-terminal fragment (105 amino acids) via a buried disulfide bond whose reduction requires prior denaturation [20].

Analytical, diagnostic and therapeutic context of CSTL1

• This paper describes VuC1, a new cystatin cDNA isolated from cowpea leaves (Vigna unguiculata (L.) Walp.). Sequence analysis revealed a multicystatin structure with two cystatin-like domains [21].
• Using an immunofluorescence technique with antibodies against rat cystatin S, an inhibitor of submandibular gland origin, cystatin-like immunoreactive material was demonstrated in the acinar cells of the exorbital lacrimal gland of the rat [13].

References