Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1

Aihua Liu, Jennifer M. Oliver-Krasinski, Doris A. Stoffers

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. Inhibition of transactivation occurs by a mechanism distinct from the classical role of POZ domains to recruit co-repressors and histone deacetylases. Understanding the functional roles of PCIF1 domains may have application to therapeutic β-cell replacement strategies involving PDX-1 for the treatment of diabetes.

Original languageEnglish (US)
Pages (from-to)6701-6706
Number of pages6
JournalFEBS Letters
Volume580
Issue number28-29
DOIs
StatePublished - Dec 11 2006
Externally publishedYes

Fingerprint

Medical problems
Transcriptional Activation
Transcription Factors
Co-Repressor Proteins
Histone Deacetylases
Insulinoma
Glucose
Homeostasis
Mutation
BTB-POZ Domain
Therapeutics

Keywords

  • Development
  • Diabetes
  • Insulin
  • Islet
  • MODY
  • Pancreas

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1. / Liu, Aihua; Oliver-Krasinski, Jennifer M.; Stoffers, Doris A.

In: FEBS Letters, Vol. 580, No. 28-29, 11.12.2006, p. 6701-6706.

Research output: Contribution to journalArticle

@article{83a2d6849f1044e485656afa376d2863,
title = "Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1",
abstract = "PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. Inhibition of transactivation occurs by a mechanism distinct from the classical role of POZ domains to recruit co-repressors and histone deacetylases. Understanding the functional roles of PCIF1 domains may have application to therapeutic β-cell replacement strategies involving PDX-1 for the treatment of diabetes.",
keywords = "Development, Diabetes, Insulin, Islet, MODY, Pancreas",
author = "Aihua Liu and Oliver-Krasinski, {Jennifer M.} and Stoffers, {Doris A.}",
year = "2006",
month = "12",
day = "11",
doi = "10.1016/j.febslet.2006.11.021",
language = "English (US)",
volume = "580",
pages = "6701--6706",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "28-29",

}

TY - JOUR

T1 - Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1

AU - Liu, Aihua

AU - Oliver-Krasinski, Jennifer M.

AU - Stoffers, Doris A.

PY - 2006/12/11

Y1 - 2006/12/11

N2 - PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. Inhibition of transactivation occurs by a mechanism distinct from the classical role of POZ domains to recruit co-repressors and histone deacetylases. Understanding the functional roles of PCIF1 domains may have application to therapeutic β-cell replacement strategies involving PDX-1 for the treatment of diabetes.

AB - PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. Inhibition of transactivation occurs by a mechanism distinct from the classical role of POZ domains to recruit co-repressors and histone deacetylases. Understanding the functional roles of PCIF1 domains may have application to therapeutic β-cell replacement strategies involving PDX-1 for the treatment of diabetes.

KW - Development

KW - Diabetes

KW - Insulin

KW - Islet

KW - MODY

KW - Pancreas

UR - http://www.scopus.com/inward/record.url?scp=33751524384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751524384&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2006.11.021

DO - 10.1016/j.febslet.2006.11.021

M3 - Article

VL - 580

SP - 6701

EP - 6706

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 28-29

ER -