Transcriptional activation of USP16 gene expression by NF?B signaling.

ABSTRACT: Ubiquitin Specific Peptidase 16 (USP16) has been reported to contribute to somatic stem-cell defects in Down syndrome. However, how this gene being regulated is largely unknown. To study the mechanism underlying USP16 gene expression, USP16 gene promoter was cloned and analyzed by luciferase assay. We identified that the 5' flanking region (-?1856?bp ~?+?468?bp) of the human USP16 gene contained the functional promotor to control its transcription. Three bona fide NF?B binding sites were found in USP16 promoter. We showed that p65 overexpression enhanced endogenous USP16 mRNA level. Furthermore, LPS and TNF?, strong activators of the NF?B pathway, upregulated the USP16 transcription. Our data demonstrate that USP16 gene expression is tightly regulated at transcription level. NF?B signaling regulates the human USP16 gene expression through three cis-acting elements. The results provide novel insights into a potential role of dysregulation of USP16 expression in Alzheimer's dementia in Down Syndrome.

SUBMITTER: Yang S 

PROVIDER: S-EPMC6937840 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature