Disease relevance of DNASE1L2

• Both DHP-1 and Hemokart-Adult caused minimal thrombocytopenia (mean always greater than 100,000/mm3) [1].

High impact information on DNASE1L2

• This protein, termed DHP-14-AB, yielded a protein with a cooperative unfolding transition (DeltaGu0=8.1 kcal/mol) and an IC50 of 27 microM when in competition with IL-4 whereas DHP-1 had no affinity for IL-4Ralpha [2].
• We describe here the characterization of the so far identified human DNase I family DNases, DNase I, DNase X, DNase gamma, and DNAS1L2 [3].
• Sequence analysis reveals that DNAS1L2 consists of seven exons [4].
• Characterization of the human DNAS1L2 gene and the molecular mechanism for its transcriptional activation induced by inflammatory cytokines [4].
• TNF-alpha and IL-1beta are found to be potent inducers of DNAS1L2 expression in keratinocytes [4].

Biological context of DNASE1L2

• DNAS1L2 is located on a 16p13.3 cosmid, while DNAS1L3 maps to 3p14.3-p21.1 by fluorescence in situ hybridization and by PCR analysis of a radiation hybrid panel [5].
• They induce DNAS1L2 activation via the NF-kappaB pathway, and an NF-kappaB binding site located within the 5' flanking region is identified as the cis-responsive element [4].
• A critical 1beta-methyl substituent shields the beta-lactam carbonyl group and serves to reduce dehydropeptidase (DHP)-1 catalysed hydrolysis of the beta-lactam, enabling ertapenem to be administered without a DHP-1 inhibitor [6].
• The antimicrobial activity of these compounds and their susceptibility to renal dehydropeptidase-1 (DHP-1) are elucidated, and their structure-activity relationships are discussed [7].

Associations of DNASE1L2 with chemical compounds

• Stability to DHP-1 was improved by methyl substitution in the isoxazoline ring, but at the expense of antibacterial activity [8].
• They are particularly active against community-acquired respiratory tract pathogens and have stabilities to DHP-1 superior to that of meropenem [9].
• The isoxazoline and isoxazolidine compounds showed potent antibacterial activity but moderate stability to human dehydropeptidase 1 (DHP-1) [8].
• The adsorption capacities of polymer-coated activated charcoal (DHP-1 and Adsorba 150C), uncharged resin (Amberlite XAD-7), anion exchange resin (Dowex-1) and polymyxin B matrix were assessed by measurement of the equilibrium adsorption isotherms for SEA [10].
• A new type of thienamycin derivatives (3a-3j, 4a, 4b), having a monothioacetal or a thioacetal side chain at the C-2 position was prepared, and the susceptibility to renal dehydropeptidase-1 (DHP-1) and the antimicrobial activity of these compounds were determined [11].

Other interactions of DNASE1L2

• DNAS1L2, a member of the DNase I-like endonuclease family, is the only divalent cation-dependent acid DNase so far identified in mammals [4].
• For many years the only notable success from such intensive research was the combination of imipenem with cilastatin, an inhibitor of the renal dipeptidase enzyme DHP-1 [12].

Analytical, diagnostic and therapeutic context of DNASE1L2

• Northern analysis revealed DNAS1L3 expression nearly exclusively in liver, while DNAS1L2 expression was detected in brain by RT-PCR [5].
• In Western blot analysis, hg303 recognizes both wild type and C-terminal Myc-His-tagged human DNase gamma, but does not cross-react with human DNase I family members, DNase I, DNase X, or DNAS1L2 [13].
• Over 4 h perfusion, DHP-1 charcoal removed 50% of the initial amount of 125I-SEA, Adsorba 150C charcoal 8.1% of SEA and Amberlite XAD-7 resin 32.5% of SEA [10].

References