Dataset Information

Regulation of xylosyltransferase I gene expression by interleukin 1? in human primary chondrocyte cells: mechanism and impact on proteoglycan synthesis.

ABSTRACT: Xylosyltransferase I (XT-I) is an essential enzyme of proteoglycan (PG) biosynthesis pathway catalyzing the initial and rate-limiting step in glycosaminoglycan chain assembly. It plays a critical role in the regulation of PG synthesis in cartilage; however, little is known about underlying mechanism. Here, we provide evidence that, in human primary chondrocytes, IL-1? regulates XT-I gene expression into an early phase of induction and a late phase of down-regulation. Based on promoter deletions, the region up to -850 bp was defined as a major element of XT-I gene displaying both constitutive and IL-1?-regulated promoter activity. Point mutation and signaling analyses revealed that IL-1?-induced promoter activity is achieved through AP-1 response elements and mediated by SAP/JNK and p38 signaling pathways. Transactivation and chromatin immunoprecipitation assays indicated that AP-1 is a potent transactivator of XT-I promoter and that IL-1?-induced activity is mediated through increased recruitment of AP-1 to the promoter. Finally, we show that Sp3 is a repressor of XT-I promoter and bring evidence that the repressive effect of IL-1? during the late phase is mediated through Sp3 recruitment to the promoter. This suggests that modulation of Sp3 in cartilage could prevent IL-1? inhibition of PG synthesis and limit tissue degradation.

SUBMITTER: Khair M

PROVIDER: S-EPMC3548487 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Regulation of xylosyltransferase I gene expression by interleukin 1β in human primary chondrocyte cells: mechanism and impact on proteoglycan synthesis.

Khair Mostafa M Bourhim Mustapha M Barré Lydia L Li Dong D Netter Patrick P Magdalou Jacques J Fournel-Gigleux Sylvie S Ouzzine Mohamed M

The Journal of biological chemistry 20121205 3

Xylosyltransferase I (XT-I) is an essential enzyme of proteoglycan (PG) biosynthesis pathway catalyzing the initial and rate-limiting step in glycosaminoglycan chain assembly. It plays a critical role in the regulation of PG synthesis in cartilage; however, little is known about underlying mechanism. Here, we provide evidence that, in human primary chondrocytes, IL-1β regulates XT-I gene expression into an early phase of induction and a late phase of down-regulation. Based on promoter deletions, ...[more]

PMID: 23223231

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Dataset Information

Regulation of xylosyltransferase I gene expression by interleukin 1? in human primary chondrocyte cells: mechanism and impact on proteoglycan synthesis.

Publications

Regulation of xylosyltransferase I gene expression by interleukin 1β in human primary chondrocyte cells: mechanism and impact on proteoglycan synthesis.

Similar Datasets

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