Abstract
Human LZIP is a transcription factor that is involved in leukocyte cell mobility. Expression of LZIP is known to differentially regulate monocyte cell migration induced by CCR1-dependent chemokines. However, its transcriptional regulation has not been characterized. 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. We identified and cloned ∼1.4 kb of the LZIP promoter from a human genomic DNA. 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. Maximal promoter activity was contained within 613 bp from the tentative transcription initiation site and was sharply reduced in a truncated construct (-338+251). This promoter sequence contained consensus NF-κB- and Sp-1-binding sites. Results from an inhibitor assay showed that NF-κB is involved in Lkn-1-induced LZIP expression, but Sp-1 is not. We also demonstrated that NF-κB binds to the LZIP promoter and that the binding is specific, as revealed by an electrophoretic mobility shift assay and a mutation analysis. Chemotaxis analysis showed that LZIP expression because of the NF-κB subfamily is specifically involved in Lkn-1-induced chemotaxis. Our findings suggest that transcription factor NF-κB plays an important role in regulation of LZIP expression, and LZIP expression regulates the monocyte cell migration induced by Lkn-1.
| Original language | English |
|---|---|
| Pages (from-to) | 11092-11100 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 282 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - 2007 Apr 13 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Regulation of human LZIP expression by NF-κB and its involvement in monocyte cell migration induced by Lkn-1. / Jang, Sung Wuk; Yoon, Suk Kim; Yoon, Rim Kim; Ho, Joong Sung; Ko, Je Sang.
In: Journal of Biological Chemistry, Vol. 282, No. 15, 13.04.2007, p. 11092-11100.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of human LZIP expression by NF-κB and its involvement in monocyte cell migration induced by Lkn-1
AU - Jang, Sung Wuk
AU - Yoon, Suk Kim
AU - Yoon, Rim Kim
AU - Ho, Joong Sung
AU - Ko, Je Sang
PY - 2007/4/13
Y1 - 2007/4/13
N2 - Human LZIP is a transcription factor that is involved in leukocyte cell mobility. Expression of LZIP is known to differentially regulate monocyte cell migration induced by CCR1-dependent chemokines. However, its transcriptional regulation has not been characterized. 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. We identified and cloned ∼1.4 kb of the LZIP promoter from a human genomic DNA. 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. Maximal promoter activity was contained within 613 bp from the tentative transcription initiation site and was sharply reduced in a truncated construct (-338+251). This promoter sequence contained consensus NF-κB- and Sp-1-binding sites. Results from an inhibitor assay showed that NF-κB is involved in Lkn-1-induced LZIP expression, but Sp-1 is not. We also demonstrated that NF-κB binds to the LZIP promoter and that the binding is specific, as revealed by an electrophoretic mobility shift assay and a mutation analysis. Chemotaxis analysis showed that LZIP expression because of the NF-κB subfamily is specifically involved in Lkn-1-induced chemotaxis. Our findings suggest that transcription factor NF-κB plays an important role in regulation of LZIP expression, and LZIP expression regulates the monocyte cell migration induced by Lkn-1.
AB - Human LZIP is a transcription factor that is involved in leukocyte cell mobility. Expression of LZIP is known to differentially regulate monocyte cell migration induced by CCR1-dependent chemokines. However, its transcriptional regulation has not been characterized. 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. We identified and cloned ∼1.4 kb of the LZIP promoter from a human genomic DNA. 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. Maximal promoter activity was contained within 613 bp from the tentative transcription initiation site and was sharply reduced in a truncated construct (-338+251). This promoter sequence contained consensus NF-κB- and Sp-1-binding sites. Results from an inhibitor assay showed that NF-κB is involved in Lkn-1-induced LZIP expression, but Sp-1 is not. We also demonstrated that NF-κB binds to the LZIP promoter and that the binding is specific, as revealed by an electrophoretic mobility shift assay and a mutation analysis. Chemotaxis analysis showed that LZIP expression because of the NF-κB subfamily is specifically involved in Lkn-1-induced chemotaxis. Our findings suggest that transcription factor NF-κB plays an important role in regulation of LZIP expression, and LZIP expression regulates the monocyte cell migration induced by Lkn-1.
UR - http://www.scopus.com/inward/record.url?scp=34249749908&partnerID=8YFLogxK
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U2 - 10.1074/jbc.M607962200
DO - 10.1074/jbc.M607962200
M3 - Article
VL - 282
SP - 11092
EP - 11100
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 15
ER -