Recombinant Mouse Kelch repeat and BTB domain-containing protein 11 (Kbtbd11) is a protein belonging to the BTB-Kelch family, characterized by its BTB/POZ domain and Kelch repeats. This protein is involved in various cellular processes, including protein-protein interactions, ubiquitination, and cell differentiation. The BTB domain facilitates dimerization and interactions with other proteins, while the Kelch repeats form a β-propeller structure that acts as a scaffold for protein interactions .
Adipogenesis: Kbtbd11 plays a significant role in adipocyte differentiation. Its expression increases during adipogenesis, and it is regulated by transcription factors like PPARγ and USF1. Knockdown of Kbtbd11 suppresses adipocyte differentiation, while overexpression promotes it .
Osteoclastogenesis: Kbtbd11 acts as a negative regulator of osteoclast differentiation by controlling the ubiquitination and degradation of NFATc1 through interaction with Cullin3 .
| Condition | Effect on Adipocyte Differentiation |
|---|---|
| Kbtbd11 Knockdown | Suppresses differentiation |
| Kbtbd11 Overexpression | Promotes differentiation |
Kbtbd11 is crucial for the early stages of adipocyte differentiation, particularly during mitotic clonal expansion (MCE). Its expression is enhanced in mice fed a high-fat diet compared to those on a standard chow diet .
| Condition | Effect on Osteoclast Differentiation |
|---|---|
| Kbtbd11 Knockdown | Enhances osteoclast formation |
| Kbtbd11 Overexpression | Impairs osteoclast differentiation |
Kbtbd11 negatively regulates osteoclast differentiation by promoting the ubiquitination and proteasomal degradation of NFATc1, a key factor in osteoclastogenesis .
Kbtbd11 interacts with several proteins, including HSC70 and HSP60, which may influence its stability or folding. Inhibitors of these proteins increase Kbtbd11 protein levels, suggesting a role in its regulation .
How does Kbtbd11 mechanistically regulate NFATc1 in osteoclastogenesis?
Kbtbd11 recruits Cullin3 to form an E3 ubiquitin ligase complex, promoting NFATc1 polyubiquitination at Lysine 684. This targets NFATc1 for proteasomal degradation, reducing its half-life from 8h to <2h . Key validation steps:
Why does Kbtbd11 overexpression fail to alter lipid accumulation in mature adipocytes?
Despite 80-fold mRNA upregulation, Kbtbd11 does not affect Pparγ or aP2 in differentiated 3T3-L1 cells . This suggests:
How to resolve contradictory data on Kbtbd11’s role in cancer vs. metabolic tissues?
Tissue-specific interactions explain discrepancies:
Why does Kbtbd11 antibody produce nonspecific bands in Western blot?
The BTB domain shares homology with KBTBD family members (e.g., KBTBD2/6). Mitigate via:
How to optimize Kbtbd11 promoter-reporter assays?
The 2.3-kb mouse promoter and 1.7-kb human promoter show maximal USF1 responsiveness . Critical elements: