Acetylation drives hepatocyte nuclear factor 1β stability by blocking proteasome‐mediated degradation

Abstract

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 ubiquitinproteasome 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. K E Y W O R D Sacetylation, hepatocyte nuclear factor 1β (HNF1β), histone deacetylase inhibitor (HDACi), protein turnover, ubiquitin-proteasome system J Cell Biochem. 2019;120:9337-9344.wileyonlinelibrary.com/journal/jcb

Ubiquitin Proteasome Gene Signatures in Ependymoma Molecular Subtypes

“…In the EPN dataset, HNF1B expression was selectively elevated by approximately 20-fold (F = 151.68, p = 1.27 × 10 −76 ) in the SP_MPE subgroup ( Figure 10 ). Acetylation of HNF1B attenuates ubiquitin-proteasomal degradation [ 28 ].…”

The acetylation modification regulates the stability of Bm30K‐15 protein and its mechanism in silkworm, Bombyx mori

“…In addition, the acetylation modification of nonhistone proteins can affect the proteasome degradation pathway by competing for ubiquitination modification, thus changing the stability of proteins and regulating the biological functions of nonhistone proteins. For example, acetylation can compete for ubiquitination of hepatocyte nuclear factor HNF1β and block ubiquitin‐mediated proteasome degradation pathway, thereby improving the protein stability of HNF1β(Lopes‐Coelho et al, 2019). It can be seen from the above that the acetylation of nonhistone proteins plays a very important biological function in the organism.…”