Bifunctional protein PCBD2 operates as a co-factor for hepatocyte nuclear factor 1β and modulates gene transcription.
Animals
Cell Line
Gene Expression Regulation
HEK293 Cells
Hepatocyte Nuclear Factor 1-beta
/ genetics
Humans
Hydro-Lyases
/ genetics
Mass Spectrometry
Mice
Models, Molecular
Potassium Channels, Inwardly Rectifying
/ genetics
Promoter Regions, Genetic
Protein Conformation
Protein Transport
Transcription, Genetic
hepatocyte nuclear factor 1β
pterin-4a-carbinolamine dehydratase 2
transcription co-factor
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
16
12
2020
received:
28
08
2020
accepted:
28
12
2020
entrez:
22
3
2021
pubmed:
23
3
2021
medline:
22
7
2021
Statut:
ppublish
Résumé
Hepatocyte nuclear factor 1β (HNF1β) is an essential transcription factor in development of the kidney, liver, and pancreas. HNF1β-mediated transcription of target genes is dependent on the cell type and the development stage. Nevertheless, the regulation of HNF1β function by enhancers and co-factors that allow this cell-specific transcription is largely unknown. To map the HNF1β interactome we performed mass spectrometry in a mouse kidney inner medullary collecting duct cell line. Pterin-4a-carbinolamine dehydratase 2 (PCBD2) was identified as a novel interaction partner of HNF1β. PCBD2 and its close homolog PCBD1 shuttle between the cytoplasm and nucleus to exert their enzymatic and transcriptional activities. Although both PCBD proteins share high sequence identity (48% and 88% in HNF1 recognition helix), their tissue expression patterns are unique. PCBD1 is most abundant in kidney and liver while PCBD2 is also abundant in lung, spleen, and adipose tissue. Using immunolocalization studies and biochemical analysis we show that in presence of HNF1β the nuclear localization of PCBD1 and PCBD2 increases significantly. Promoter luciferase assays demonstrate that co-factors PCBD1 and PCBD2 differentially regulate the ability of HNF1β to activate the promoters of transcriptional targets important in renal electrolyte homeostasis. Deleting the N-terminal sequence of PCBD2, not found in PCBD1, diminished the differential effects of the co-factors on HNF1β activity. All together these results indicate that PCBD1 and PCBD2 can exert different effects on HNF1β-mediated transcription. Future studies should confirm whether these unique co-factor activities also apply to HNF1β-target genes involved in additional processes besides ion transport in the kidney.
Identifiants
pubmed: 33749890
doi: 10.1096/fj.202002022R
doi:
Substances chimiques
HNF1B protein, human
0
KCNJ16 protein, human
0
Potassium Channels, Inwardly Rectifying
0
Hepatocyte Nuclear Factor 1-beta
138674-15-4
Hydro-Lyases
EC 4.2.1.-
PCBD2 protein, human
EC 4.2.1.-
pterin-4a-carbinolamine dehydratase
EC 4.2.1.96
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21366Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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