Acetylation drives hepatocyte nuclear factor 1β stability by blocking proteasome-mediated degradation.
Filipa Lopes-CoelhoFernanda SilvaAna HipólitoBruno A CardosoJacinta SerpaPublished in: Journal of cellular biochemistry (2018)
Hepatocyte nuclear factor 1β (HNF1β) is mostly expressed in the liver, but is also expressed in other organs, like kidney, pancreas and genitourinary tract. In fact, HNF1β, a member of the superfamily of homeodomain-containing transcription factors, has been described as a hallmark in clear cell carcinomas. However, its role as an oncogene or as tumor suppressor gene remains controversial. Here, we disclose a mechanism of HNF1β stabilization and degradation, using human HNF1β-expressing cell lines of ovarian clear cell carcinoma (ES2), hepatocellular carcinoma (HEPG2), and normal immortalized kidney tubular cells (HK2). We show that increased levels of HNF1β is concomitant with an increase in the acetylation load and protein stabilization by interfering with the ubiquitin-proteasome degradation system. This study reinforces that acetylation, besides their role in regulating chromatin conformation and gene expression, could also act in the action, turnover and stability of proteins essential for the survival and progression of certain cancer types.
Keyphrases
- nuclear factor
- toll like receptor
- gene expression
- transcription factor
- endothelial cells
- genome wide
- genome wide identification
- dna methylation
- clear cell
- histone deacetylase
- cell cycle arrest
- papillary thyroid
- inflammatory response
- high glucose
- liver injury
- immune response
- cell death
- copy number
- squamous cell carcinoma
- molecular dynamics simulations
- binding protein
- signaling pathway