Characterization of the human DNAS1L2 gene and the molecular mechanism for its transcriptional activation induced by inflammatory cytokines.
DNAS1L2, a member of the DNase I-like endonuclease family, is the only divalent cation-dependent acid DNase so far identified in mammals. The presence of a proline-rich domain (PRD) is its unique feature among family members. We found that a novel transcript encoding a short product, DNAS1L2-S, is expressed in peripheral blood leukocytes. Although DNAS1L2-S lacks the PRD, its enzymatic properties are apparently the same as those of the previously identified long form, DNAS1L2-L. Sequence analysis reveals that DNAS1L2 consists of seven exons. The exon/intron boundaries agree with the GT/AG rule with one exception: GC replaces GT at the 5' splice site in the sixth intron. TNF-alpha and IL-1beta are found to be potent inducers of DNAS1L2 expression in keratinocytes. 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.
Shiokawa
Daisuke
D
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Matsushita
Tokiyoshi
T
Kobayashi
Takanobu
T
Matsumoto
Yoshifumi
Y
Tanuma
Sei-Ichi
S
D024506:5' Flanking Region / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D003850:Deoxyribonuclease I / Q000096:biosynthesis / Q000235:genetics*; D003851:Deoxyribonucleases / Q000235:genetics*; D004706:Endodeoxyribonucleases; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015603:Keratinocytes / Q000502:physiology; D007962:Leukocytes / Q000502:physiology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; C107519:DNASE1L2 protein, human; D003850:Deoxyribonuclease I