PMID- 27017486
OWN - NLM
STAT- MEDLINE
DCOM- 20170117
LR  - 20210930
IS  - 1432-5233 (Electronic)
IS  - 0940-5429 (Linking)
VI  - 53
IP  - 4
DP  - 2016 Aug
TI  - Phosphorylation of MafA enhances interaction with Beta2/NeuroD1.
PG  - 651-60
LID - 10.1007/s00592-016-0853-1 [doi]
AB  - AIMS: MafA is a critical regulator of insulin expression and mature beta-cell 
      function. MafA binds to the insulin promoter through its carboxyl-terminal basic 
      domain-leucine zipper (bZip) region and activates transcription synergistically 
      with the beta-cell-enriched transactivators Beta2 (NeuroD1) and Pdx1. MafA protein 
      is highly phosphorylated in beta-cells, and phosphorylation at multiple sites within 
      its amino-terminal region is critical for its DNA-binding and transactivating 
      abilities, as well as for regulation of its degradation. Here, we investigated 
      whether phosphorylation of MafA affects its interaction with Beta2. METHODS: By 
      mutational analysis, we identified interaction domains of MafA and Beta2. Using 
      in situ proximity ligation assay (PLA), we explored mechanism of 
      phosphorylation-dependent binding of MafA with Beta2. We also searched for a 
      pathophysiological condition that would induce lower levels of MafA 
      phosphorylation. RESULTS: Mutational analysis revealed that the phosphorylation 
      sites within the amino-terminal region of MafA were not necessary for interaction 
      with Beta2. In situ PLA suggested that phosphorylation induces conformational or 
      configurational changes in MafA, thereby regulating the interaction with Beta2. 
      We also found that long-term culture of the MIN6 insulinoma cell line under 
      high-glucose conditions resulted in a decrease in beta-cell-specific transcripts 
      including insulin, along with a decrease in MafA phosphorylation and DNA binding. 
      CONCLUSION: Phosphorylation of MafA plays a critical role in beta-cell function by 
      regulating multiple functionalities, including binding to DNA, interaction with 
      Beta2, and transactivation.
FAU - Han, Song-Iee
AU  - Han SI
AD  - Laboratory of Molecular Medical Bioscience, Graduate School of Medical Life 
      Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, 
      230-0045, Japan.
AD  - Department of Internal Medicine (Endocrinology and Metabolism), Graduate School 
      of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 
      305-8575, Japan.
FAU - Tsunekage, Yukino
AU  - Tsunekage Y
AD  - Laboratory of Molecular Medical Bioscience, Graduate School of Medical Life 
      Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, 
      230-0045, Japan.
FAU - Kataoka, Kohsuke
AU  - Kataoka K
AUID- ORCID: 0000-0001-5685-3908
AD  - Laboratory of Molecular Medical Bioscience, Graduate School of Medical Life 
      Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, 
      230-0045, Japan. kkataoka@tsurumi.yokohama-cu.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20160326
PL  - Germany
TA  - Acta Diabetol
JT  - Acta diabetologica
JID - 9200299
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Insulin)
RN  - 0 (MafB Transcription Factor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 169238-82-8 (Neurogenic differentiation factor 1)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/*metabolism
MH  - Binding Sites
MH  - Cell Line
MH  - Gene Expression Regulation
MH  - Insulin/metabolism
MH  - Insulin-Secreting Cells/*metabolism
MH  - MafB Transcription Factor/*metabolism
MH  - Mice
MH  - Nerve Tissue Proteins/*metabolism
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
OTO - NOTNLM
OT  - Beta2/NeuroD1
OT  - Insulin
OT  - MafA
OT  - Phosphorylation
OT  - Transcriptional regulation
EDAT- 2016/03/28 06:00
MHDA- 2017/01/18 06:00
CRDT- 2016/03/28 06:00
PHST- 2015/12/29 00:00 [received]
PHST- 2016/03/02 00:00 [accepted]
PHST- 2016/03/28 06:00 [entrez]
PHST- 2016/03/28 06:00 [pubmed]
PHST- 2017/01/18 06:00 [medline]
AID - 10.1007/s00592-016-0853-1 [pii]
AID - 10.1007/s00592-016-0853-1 [doi]
PST - ppublish
SO  - Acta Diabetol. 2016 Aug;53(4):651-60. doi: 10.1007/s00592-016-0853-1. Epub 2016 
      Mar 26.