Nevertheless, recognizing the related sickness pathomechanism is a challenge. Also, while the ailments reported thus far are all due to mutations that cause MBTPS2 to lose function, other variants that cause MBTPS2 to be hyperactive have not been examined. Additionally, MBTPS2 causes different diseases, possibly illustrating the pleiotropic nature of the protein. In addition, we discovered the identity of both of S2P's catalytic active sites, an essential finding as the activity of the proteolysis as well as the pathogenesis of MBTPS2-caused illnesses seems to be connected to the molecular and biochemical features of the catalytic sites. With this newfound information from biochemical and structural biology, S2P's proteolytic action through peptide bond hydrolysis can occur in the membrane, providing a conceptual framework for appreciating S2P's roles in other aspects, and showing that many other substrates rely on S2P for their survival. The protease has developed from an element of the SREBP cleavage machinery to an important regulator of several cellular processes, especially in health and sickness. Since the identification of MBTPS2 in 1997, tremendous progress has been made in determining the protease's functions. Our findings suggest that transcription factor NF-kappaB plays an important role in regulation of LZIP expression, and LZIP expression regulates the monocyte cell migration induced by Lkn-1. Chemotaxis analysis showed that LZIP expression because of the NF-kappaB subfamily is specifically involved in Lkn-1-induced chemotaxis. We also demonstrated that NF-kappaB binds to the LZIP promoter and that the binding is specific, as revealed by an electrophoretic mobility shift assay and a mutation analysis. Results from an inhibitor assay showed that NF-kappaB is involved in Lkn-1-induced LZIP expression, but Sp-1 is not. This promoter sequence contained consensus NF-kappaB- and Sp-1-binding sites. Maximal promoter activity was contained within 613 bp from the tentative transcription initiation site and was sharply reduced in a truncated construct (-338/+251). To identify regulatory elements controlling restricted expression of LZIP, deletion mutants were constructed from the 1469-bp LZIP promoter region (-1219/+251) linked to the luciferase reporter gene. We identified and cloned approximately 1.4 kb of the LZIP promoter from a human genomic DNA. Our results indicate that Lkn-1 induces LZIP expression in a time- and dose-dependent manner, and the induction of LZIP shows an immediate early response to Lkn-1. However, its transcriptional regulation has not been characterized. Expression of LZIP is known to differentially regulate monocyte cell migration induced by CCR1-dependent chemokines. Human LZIP is a transcription factor that is involved in leukocyte cell mobility.
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