PMID- 36030658
OWN - NLM
STAT- MEDLINE
DCOM- 20220913
LR  - 20221012
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 627
DP  - 2022 Oct 30
TI  - TRAF2 regulates the protein stability of HIPK2.
PG  - 97-102
LID - S0006-291X(22)01150-0 [pii]
LID - 10.1016/j.bbrc.2022.08.031 [doi]
AB  - A nuclear serine/threonine kinase homeodomain-interacting protein kinase 2 
      (HIPK2) is a critical regulator of development and DNA damage response. HIPK2 can 
      induce apoptosis under cellular stress conditions and thus its protein level is 
      maintained low by constant proteasomal degradation. In the present study, we 
      present evidence that TNF receptor-associated factor 2 (TRAF2) regulates the 
      protein stability of HIPK2. Overexpression of TRAF2 decreased while its knockdown 
      increased the HIPK2 protein level. The TRAF2-mediated decrease in HIPK2 protein 
      expression was blocked by proteasomal inhibitor. In addition, TRAF2 decreased the 
      protein half-life of HIPK2. We found that HIPK2 and TRAF2 co-immunoprecipitated. 
      Interestingly, the co-immunoprecipitation was reduced while HIPK2 protein level 
      increased following TNFalpha treatment, suggesting TNFalpha induced dissociation of TRAF2 
      from HIPK2 to accumulate HIPK2. Inhibition of HIPK2 partially suppressed 
      TNFalpha-induced cell death, indicating that the accumulated HIPK2 may contribute to 
      the TNFalpha-induced cell death. Our results suggest that TRAF2 can regulate 
      proapoptotic function of HIPK2 by promoting proteasomal degradation.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Lee, Impyo
AU  - Lee I
AD  - Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, 
      05006, Republic of Korea.
FAU - Kim, Chae-Eun
AU  - Kim CE
AD  - Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, 
      05006, Republic of Korea.
FAU - Cho, Harim
AU  - Cho H
AD  - Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, 
      05006, Republic of Korea.
FAU - Im, Hana
AU  - Im H
AD  - Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, 
      05006, Republic of Korea.
FAU - Shin, Ki Soon
AU  - Shin KS
AD  - Department of Biology, Kyung Hee University, Seoul, 02447, Republic of Korea; 
      Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, 
      02447, Republic of Korea.
FAU - Kang, Shin Jung
AU  - Kang SJ
AD  - Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, 
      05006, Republic of Korea. Electronic address: sjkang@sejong.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220823
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Apoptosis
MH  - *Protein Serine-Threonine Kinases/genetics
MH  - Protein Stability
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - *Tumor Necrosis Factor-alpha/metabolism/pharmacology
MH  - Ubiquitin-Protein Ligases/metabolism
OTO - NOTNLM
OT  - HIPK2
OT  - Proteasomal degradation
OT  - TNFalpha
OT  - TRAF2
OT  - Ubiquitination
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/08/29 06:00
MHDA- 2022/09/14 06:00
CRDT- 2022/08/28 18:13
PHST- 2022/08/01 00:00 [received]
PHST- 2022/08/11 00:00 [accepted]
PHST- 2022/08/29 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2022/08/28 18:13 [entrez]
AID - S0006-291X(22)01150-0 [pii]
AID - 10.1016/j.bbrc.2022.08.031 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2022 Oct 30;627:97-102. doi: 
      10.1016/j.bbrc.2022.08.031. Epub 2022 Aug 23.