PMID- 29933112
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20201209
IS  - 1873-2763 (Electronic)
IS  - 1873-2763 (Linking)
VI  - 114
DP  - 2018 Sep
TI  - BCL3 regulates RANKL-induced osteoclastogenesis by interacting with TRAF6 in bone 
      marrow-derived macrophages.
PG  - 257-267
LID - S8756-3282(18)30247-3 [pii]
LID - 10.1016/j.bone.2018.06.015 [doi]
AB  - OBJECTIVE: Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an 
      essential component of the signaling complex that mediates osteoclastogenesis. As 
      an adaptor protein of E3 ligase function, TRAF6 regulates NF-kappaB signaling via 
      TAK1 and I-kappaB kinase (IKK) activation. Here, we investigated novel mechanisms by 
      which TRAF6 signaling is regulated under receptor activator of nuclear factor-kappaB 
      ligand (RANKL)-induced osteoclastogenesis. DESIGN: A yeast two-hybrid screen 
      system identified cellular factors that interact with TRAF6. The interactions 
      were confirmed by glutathione S-transferase pull-down and co-immunoprecipitation 
      assays, followed by immuno-blotting. The role of TRAF6 in bone growth and 
      remodeling was determined by osteoclast differentiation and bone-resorption pit 
      assays. Regulatory mechanisms were examined by co-immunoprecipitation, 
      immuno-blotting, real-time polymerase chain reaction, and luciferase reporter 
      assays. RESULTS: We show that B-cell chronic lymphatic leukemia protein 3 (BCL3) 
      interacts with TRAF6 through its ankyrin-repeat domain and inhibits 
      osteoclastogenesis in bone marrow derived macrophages (BMDMs). Further, TRAF6 
      interacts with CYLD to mediate BCL3 deubiquitination, which facilitates the 
      cytoplasmic accumulation of BCL3 and represses BCL3 and p50 complex-mediated 
      cyclin D1 transcription. CONCLUSIONS: TRAF6 promotes RANKL-induced 
      osteoclastogenesis by regulating novel non-canonical NF-kappaB signaling via BCL3 
      deubiquitination, indicating that BCL3 provides valuable insights into bone 
      loss-associated diseases.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Wang, Kun
AU  - Wang K
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Li, Shuai
AU  - Li S
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Gao, Yong
AU  - Gao Y
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Feng, Xiaobo
AU  - Feng X
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Liu, Wei
AU  - Liu W
AD  - Department of Orthopedics, First Hospital of Wuhan, Wuhan 430022, China.
FAU - Luo, Rongjin
AU  - Luo R
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Song, Yu
AU  - Song Y
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Ji Tu
AU  - Ji Tu
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Liu, Yingle
AU  - Liu Y
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan 430072, China. Electronic address: liuyingle1977@sina.com.
FAU - Yang, Cao
AU  - Yang C
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China. Electronic address: 
      yangcao1971@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180619
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (B-Cell Lymphoma 3 Protein)
RN  - 0 (BCL3 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RANK Ligand)
RN  - 0 (TNF Receptor-Associated Factor 6)
RN  - 0 (TNFSF11 protein, human)
RN  - 0 (Tifab protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - B-Cell Lymphoma 3 Protein
MH  - HEK293 Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Macrophages/*metabolism
MH  - Osteoclasts/*metabolism
MH  - Osteogenesis/*physiology
MH  - Protein Binding/physiology
MH  - Proto-Oncogene Proteins/*metabolism
MH  - RANK Ligand/*metabolism
MH  - TNF Receptor-Associated Factor 6/*metabolism
MH  - Transcription Factors/*metabolism
OTO - NOTNLM
OT  - B-cell chronic lymphatic leukemia protein 3
OT  - Osteoclastogenesis
OT  - Tumor necrosis factor receptor-associated factor 6
EDAT- 2018/06/23 06:00
MHDA- 2019/07/23 06:00
CRDT- 2018/06/23 06:00
PHST- 2018/01/22 00:00 [received]
PHST- 2018/06/15 00:00 [revised]
PHST- 2018/06/18 00:00 [accepted]
PHST- 2018/06/23 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
PHST- 2018/06/23 06:00 [entrez]
AID - S8756-3282(18)30247-3 [pii]
AID - 10.1016/j.bone.2018.06.015 [doi]
PST - ppublish
SO  - Bone. 2018 Sep;114:257-267. doi: 10.1016/j.bone.2018.06.015. Epub 2018 Jun 19.