PMID- 33155406
OWN - NLM
STAT- MEDLINE
DCOM- 20210713
LR  - 20220102
IS  - 1930-739X (Electronic)
IS  - 1930-7381 (Print)
IS  - 1930-7381 (Linking)
VI  - 29
IP  - 1
DP  - 2021 Jan
TI  - SIAH2 is Expressed in Adipocyte Precursor Cells and Interacts with EBF1 and 
      ZFP521 to Promote Adipogenesis.
PG  - 98-107
LID - 10.1002/oby.23013 [doi]
AB  - OBJECTIVE: Expression of zinc finger protein 423 (ZFP423), a key proadipogenic 
      transcription factor in adipocyte precursor cells, is regulated by interaction of 
      the proadipogenic early B-cell factor 1 (EBF1) and antiadipogenic ZFP521. The 
      ubiquitin ligase seven-in-absentia homolog 2 (SIAH2) targets ZFP521 for 
      degradation. This study asked whether SIAH2 is expressed in adipocyte precursor 
      cells and whether SIAH2 interacts with ZFP521 and EBF1 to regulate ZFP521 protein 
      levels during adipogenesis. METHODS: SIAH2 expression in precursor cells was 
      assessed in primary cells and tissues from wild-type and SIAH2 null mice fed a 
      control or high-fat diet. Primary cells, 3T3-L1 preadipocytes, and HEK293T cells 
      were used to analyze Siah2, Ebf1, and Zfp521 expression and SIAH2-mediated 
      changes in ZFP521 and EBF1 protein levels. RESULTS: Siah2 is expressed in 
      platelet-derived growth factor receptor alpha (PDGFRalpha)(+) and stem cell antigen-1 
      (SCA1)(+) adipocyte precursor cells. SIAH2 depletion reduces Ebf1 gene expression 
      and increases EBF1 protein levels in early but not late adipogenesis. In early 
      adipogenesis, SIAH2 forms a protein complex with EBF1 and ZFP521 to enhance 
      SIAH2-mediated ubiquitylation and degradation of ZFP521 while increasing EBF1 
      protein levels. CONCLUSIONS: Siah2 is expressed in PDGFRalpha+ adipocyte precursor 
      cells and is linked to precursor cell commitment to adipogenesis by interacting 
      with EBF1 and ZFP521 proteins to target the antiadipogenic ZFP521 for 
      degradation.
CI  - (c) 2020 The Obesity Society.
FAU - Dang, Thanh N
AU  - Dang TN
AUID- ORCID: 0000-0003-1020-0930
AD  - Pennington Biomedical Research Center, Louisiana State University System, Baton 
      Rouge, Louisiana, USA.
FAU - Taylor, Jessica L
AU  - Taylor JL
AD  - Pennington Biomedical Research Center, Louisiana State University System, Baton 
      Rouge, Louisiana, USA.
FAU - Kilroy, Gail
AU  - Kilroy G
AD  - Pennington Biomedical Research Center, Louisiana State University System, Baton 
      Rouge, Louisiana, USA.
FAU - Yu, Yongmei
AU  - Yu Y
AD  - Pennington Biomedical Research Center, Louisiana State University System, Baton 
      Rouge, Louisiana, USA.
FAU - Burk, David H
AU  - Burk DH
AD  - Pennington Biomedical Research Center, Louisiana State University System, Baton 
      Rouge, Louisiana, USA.
FAU - Floyd, Z Elizabeth
AU  - Floyd ZE
AUID- ORCID: 0000-0002-3002-6186
AD  - Pennington Biomedical Research Center, Louisiana State University System, Baton 
      Rouge, Louisiana, USA.
LA  - eng
GR  - P30 DK072476/DK/NIDDK NIH HHS/United States
GR  - R01 DK099625/DK/NIDDK NIH HHS/United States
GR  - T32 AT004094/AT/NCCIH NIH HHS/United States
GR  - P30 GM118430/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201106
PL  - United States
TA  - Obesity (Silver Spring)
JT  - Obesity (Silver Spring, Md.)
JID - 101264860
RN  - 0 (EBF1 protein, human)
RN  - 0 (Ebf1 protein, mouse)
RN  - 0 (Evi3 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.2.27 (Siah2 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/cytology/*metabolism
MH  - *Adipogenesis
MH  - Animals
MH  - Gene Expression
MH  - Gene Expression Regulation
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Ubiquitin-Protein Ligases/*metabolism
PMC - PMC7902405
MID - NIHMS1630780
COIS- DISCLOSURE: The authors declared no conflict of interest.
EDAT- 2020/11/07 06:00
MHDA- 2021/07/14 06:00
PMCR- 2022/01/01
CRDT- 2020/11/06 06:05
PHST- 2020/04/16 00:00 [received]
PHST- 2020/08/07 00:00 [revised]
PHST- 2020/08/10 00:00 [accepted]
PHST- 2020/11/07 06:00 [pubmed]
PHST- 2021/07/14 06:00 [medline]
PHST- 2020/11/06 06:05 [entrez]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.1002/oby.23013 [doi]
PST - ppublish
SO  - Obesity (Silver Spring). 2021 Jan;29(1):98-107. doi: 10.1002/oby.23013. Epub 2020 
      Nov 6.