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

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
Pages (from-to)9337-9344
JournalJournal Of Cellular Biochemistry
Volume120
Issue number6
DOIs
Publication statusPublished - Jun 2019

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Hepatocyte Nuclear Factor 1
Acetylation
Proteasome Endopeptidase Complex
Degradation
Cells
Stabilization
Carcinoma
Kidney
Protein Stability
Ubiquitin
Tumor Suppressor Genes
Oncogenes
Gene expression
Liver
Chromatin
Conformations
Tumors
Pancreas
Hepatocellular Carcinoma
Proteins

Keywords

  • acetylation
  • hepatocyte nuclear factor 1β (HNF1β)
  • histone deacetylase inhibitor (HDACi)
  • protein turnover
  • ubiquitin-proteasome system

Cite this

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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 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.",
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author = "Filipa Lopes-Coelho and Fernanda Silva and Ana Hip{\'o}lito and Cardoso, {Bruno A.} and Jacinta Serpa",
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AU - Lopes-Coelho, Filipa

AU - Silva, Fernanda

AU - Hipólito, Ana

AU - Cardoso, Bruno A.

AU - Serpa, Jacinta

PY - 2019/6

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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)

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KW - protein turnover

KW - ubiquitin-proteasome system

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