| First Author | Yu L | Year | 2008 |
| Journal | Blood | Volume | 111 |
| Issue | 9 | Pages | 4617-26 |
| PubMed ID | 18292289 | Mgi Jnum | J:134341 |
| Mgi Id | MGI:3785342 | Doi | 10.1182/blood-2007-10-121137 |
| Citation | Yu L, et al. (2008) Proteasome-dependent autoregulation of Bruton tyrosine kinase (Btk) promoter via NF-{kappa}B. Blood 111(9):4617-26 |
| abstractText | Bruton tyrosine kinase (Btk) is critical for B-cell development. Btk regulates a plethora of signaling proteins, among them nuclear factor-[kappa]B (NF-kappaB). Activation of NF-kappaB is a hallmark of B cells, and NF-kappaB signaling is severely compromised in Btk deficiency. We here present strong evidence indicating that NF-kappaB is required for efficient transcription of the Btk gene. First, we found that proteasome blockers and inhibitors of NF-kappaB signaling suppress Btk transcription and intracellular expression. Similar to Btk, proteasome inhibitors also reduced the expression of other members of this family of kinases, Itk, Bmx, and Tec. Second, 2 functional NF-kappaB-binding sites were found in the Btk promoter. Moreover, in live mice, by hydrodynamic transfection, we show that bortezomib (a blocker of proteasomes and NF-kappaB signaling), as well as NF-kappaB binding sequence-oligonucleotide decoys block Btk transcription. We also demonstrate that Btk induces NF-kappaB activity in mice. Collectively, we show that Btk uses a positive autoregulatory feedback mechanism to stimulate transcription from its own promoter via NF-kappaB. |
