TY - JOUR
T1 - Acetylation drives hepatocyte nuclear factor 1β stability by blocking proteasome-mediated degradation
AU - Lopes-Coelho, Filipa
AU - Silva, Fernanda
AU - Hipólito, Ana
AU - Cardoso, Bruno A.
AU - Serpa, Jacinta
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - acetylation
KW - hepatocyte nuclear factor 1β (HNF1β)
KW - histone deacetylase inhibitor (HDACi)
KW - protein turnover
KW - ubiquitin-proteasome system
UR - http://www.scopus.com/inward/record.url?scp=85058038927&partnerID=8YFLogxK
U2 - 10.1002/jcb.28209
DO - 10.1002/jcb.28209
M3 - Article
C2 - 30525249
AN - SCOPUS:85058038927
SN - 0730-2312
VL - 120
SP - 9337
EP - 9344
JO - Journal Of Cellular Biochemistry
JF - Journal Of Cellular Biochemistry
IS - 6
ER -