PMID- 21543335
OWN - NLM
STAT- MEDLINE
DCOM- 20110830
LR  - 20240510
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 25
DP  - 2011 Jun 24
TI  - Modulation of the transactivation function and stability of Kruppel-like zinc 
      finger protein Gli-similar 3 (Glis3) by Suppressor of Fused.
PG  - 22077-89
LID - 10.1074/jbc.M111.224964 [doi]
AB  - Glis3 is a member of the Glis subfamily of Kruppel-like zinc finger transcription 
      factors. Recently, Glis3 has been linked to both type I and type II diabetes and 
      shown to positively regulate insulin gene expression. In this study, we have 
      identified a region within the N terminus of Glis3 that shares high levels of 
      homology with the Cubitus interruptus (Ci)/Gli family of proteins. We 
      demonstrated that Glis3 interacts with Suppressor of Fused (SUFU), which involves 
      a VYGHF motif located within this conserved region. We further showed that SUFU 
      is able to inhibit the activation of the insulin promoter by Glis3 but not the 
      activation by a Glis3 mutant deficient in its ability to bind SUFU, suggesting 
      that the inhibitory effect is dependent on the interaction between the two 
      proteins. Exogenous SUFU did not affect the nuclear localization of Glis3; 
      however, Glis3 promoted the nuclear accumulation of SUFU. Additionally, we 
      demonstrated that SUFU stabilizes Glis3 in part by antagonizing the Glis3 
      association with a Cullin 3-based E3 ubiquitin ligase that promotes the 
      ubiquitination and degradation of Glis3. This is the first reported instance of 
      Glis3 interacting with SUFU and suggests a novel role for SUFU in the modulation 
      of Glis3 signaling. Given the critical role of Glis3 in pancreatic beta-cell 
      generation and maintenance, the elevated Glis3 expression in several cancers, and 
      the established role of SUFU as a tumor suppressor, these data provide further 
      insight into Glis3 regulation and its function in development and disease.
FAU - ZeRuth, Gary T
AU  - ZeRuth GT
AD  - Cell Biology Section, Division of Intramural Research, NIEHS, National Institutes 
      of Health, Research Triangle Park, North Carolina 27709, USA.
FAU - Yang, Xiao-Ping
AU  - Yang XP
FAU - Jetten, Anton M
AU  - Jetten AM
LA  - eng
GR  - Z01 ES100485/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20110504
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CUL3 protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GLIS3 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Repressor Proteins)
RN  - 0 (SUFU protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Nucleus/metabolism
MH  - Cullin Proteins/metabolism
MH  - DNA-Binding Proteins
MH  - HEK293 Cells
MH  - Humans
MH  - Insulin/genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Stability
MH  - Rats
MH  - Repressor Proteins/*metabolism
MH  - Signal Transduction
MH  - Trans-Activators
MH  - Transcription Factors/*chemistry/*metabolism
MH  - *Transcriptional Activation
PMC - PMC3121352
EDAT- 2011/05/06 06:00
MHDA- 2011/08/31 06:00
PMCR- 2012/06/24
CRDT- 2011/05/06 06:00
PHST- 2011/05/06 06:00 [entrez]
PHST- 2011/05/06 06:00 [pubmed]
PHST- 2011/08/31 06:00 [medline]
PHST- 2012/06/24 00:00 [pmc-release]
AID - S0021-9258(19)48915-1 [pii]
AID - M111.224964 [pii]
AID - 10.1074/jbc.M111.224964 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Jun 24;286(25):22077-89. doi: 10.1074/jbc.M111.224964. Epub 
      2011 May 4.