PMID- 31433867
OWN - NLM
STAT- MEDLINE
DCOM- 20200910
LR  - 20200910
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Print)
IS  - 0884-0431 (Linking)
VI  - 34
IP  - 12
DP  - 2019 Dec
TI  - Hop2 Interacts with ATF4 to Promote Osteoblast Differentiation.
PG  - 2287-2300
LID - 10.1002/jbmr.3857 [doi]
AB  - Activating transcription factor 4 (ATF4) is a member of the basic leucine zipper 
      (bZip) transcription factor family required for the terminal differentiation of 
      osteoblasts. Despite its critical importance as one of the three main osteoblast 
      differentiation transcription factors, regulators of osteoblast terminal 
      maturation remain poorly defined. Here we report the identification of homologous 
      pairing protein 2 (Hop2) as a dimerization partner of ATF4 in osteoblasts via the 
      yeast two-hybrid system. Deletional mapping revealed that the Zip domain of Hop2 
      is necessary and sufficient to bind ATF4 and to enhance ATF4-dependent 
      transcription. Ectopic Hop2 expression in preosteoblasts increased endogenous 
      ATF4 protein content and accelerated osteoblast differentiation. Mice lacking 
      Hop2 (Hop2(-/-) ) have a normal stature but exhibit an osteopenic phenotype 
      similar to the one observed in Atf4(-/-) mice, albeit milder, which is associated 
      with decreased Osteocalcin mRNA expression and reduced type I collagen synthesis. 
      Compound heterozygous mice (Atf4(+/-) :Hop2(+/-) ) display identical skeletal 
      defects to those found in Hop2(-/-) mice. These results indicate that Hop2 plays 
      a previous unknown role as a determinant of osteoblast maturation via its 
      regulation of ATF4 transcriptional activity. Our work for the first time reveals 
      a function of Hop2 beyond its role in guiding the alignment of homologous 
      chromosomes. (c) 2019 American Society for Bone and Mineral Research.
CI  - (c) 2019 American Society for Bone and Mineral Research.
FAU - Zhang, Yang
AU  - Zhang Y
AD  - Pediatric Research Center, Department of Pediatrics, UTHealth McGovern Medical 
      School, Houston, TX, USA.
AD  - Department of Orthopaedic Surgery, Division of Orthopaedics, Nanfang Hospital, 
      Southern Medical University, Guangzhou, China.
FAU - Lin, Tonghui
AU  - Lin T
AD  - Pediatric Research Center, Department of Pediatrics, UTHealth McGovern Medical 
      School, Houston, TX, USA.
FAU - Lian, Na
AU  - Lian N
AD  - Pediatric Research Center, Department of Pediatrics, UTHealth McGovern Medical 
      School, Houston, TX, USA.
FAU - Tao, Huan
AU  - Tao H
AD  - Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt 
      University Medical Center, Nashville, TX, USA.
FAU - Li, Cong
AU  - Li C
AD  - Pediatric Research Center, Department of Pediatrics, UTHealth McGovern Medical 
      School, Houston, TX, USA.
FAU - Li, Lingzhen
AU  - Li L
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      TX, USA.
FAU - Yang, Xiangli
AU  - Yang X
AUID- ORCID: 0000-0002-2333-8747
AD  - Pediatric Research Center, Department of Pediatrics, UTHealth McGovern Medical 
      School, Houston, TX, USA.
LA  - eng
GR  - R01 AR055972/AR/NIAMS NIH HHS/United States
GR  - R01 AR067303/AR/NIAMS NIH HHS/United States
GR  - R01AR067303/GF/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191104
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Hop2 protein, mouse)
RN  - 145891-90-3 (Activating Transcription Factor 4)
SB  - IM
MH  - Activating Transcription Factor 4/genetics/*metabolism
MH  - Animals
MH  - Bone Diseases, Metabolic/metabolism/pathology
MH  - Cell Cycle Proteins/deficiency/genetics/*metabolism
MH  - *Cell Differentiation
MH  - Cell Line
MH  - Epistasis, Genetic
MH  - Mice
MH  - Models, Biological
MH  - Osteoblasts/*cytology/*metabolism
MH  - Phenotype
MH  - Protein Binding
MH  - Transcription, Genetic
PMC - PMC7422940
MID - NIHMS1612556
OTO - NOTNLM
OT  - ATF4
OT  - DIFFERENTIATION
OT  - HOP2
OT  - OSTEOBLAST
OT  - TRANSCRIPTION FACTOR
COIS- Disclosures All authors state that they have no conflicts of interest.
EDAT- 2019/08/23 06:00
MHDA- 2020/09/12 06:00
PMCR- 2020/08/12
CRDT- 2019/08/22 06:00
PHST- 2019/02/11 00:00 [received]
PHST- 2019/07/25 00:00 [revised]
PHST- 2019/08/14 00:00 [accepted]
PHST- 2019/08/23 06:00 [pubmed]
PHST- 2020/09/12 06:00 [medline]
PHST- 2019/08/22 06:00 [entrez]
PHST- 2020/08/12 00:00 [pmc-release]
AID - 10.1002/jbmr.3857 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2019 Dec;34(12):2287-2300. doi: 10.1002/jbmr.3857. Epub 2019 
      Nov 4.