PMID- 28174693
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 2211-5463 (Print)
IS  - 2211-5463 (Electronic)
IS  - 2211-5463 (Linking)
VI  - 7
IP  - 2
DP  - 2017 Feb
TI  - Fanconi anemia protein FANCD2 is activated by AICAR, a modulator of AMPK and 
      cellular energy metabolism.
PG  - 284-292
LID - 10.1002/2211-5463.12185 [doi]
AB  - FANCD2 is a pivotal molecule in the pathogenesis of Fanconi anemia (FA), an 
      autosomal recessive human syndrome with diverse clinical phenotypes, including 
      cancer predisposition, short stature, and hematological abnormalities. In our 
      previous study, we detected the functional association of FANC proteins, whose 
      mutations are responsible for the onset of FA, with AMPK in response to DNA 
      interstrand crosslinking lesions. Because AMPK is well known as a critical 
      sensing molecule for cellular energy levels, we checked whether FANCD2 activation 
      occurs after treatments affecting AMPK and/or cellular energy status. Among the 
      treatments tested, AMPK-activating 5-aminoimidazole-4-carboxamide-ribonucleoside 
      (AICAR) induced monoubiquitination and nuclear foci formation of FANCD2, which 
      are biomarkers of FANCD2 activation. FANCD2 activation was abolished by 
      treatments with Compound C, an AMPK inhibitor, or after AMPKalpha1 knockdown, 
      substantiating the involvement of AMPK in AICAR-induced FANCD2 activation. 
      Similarly, FANCA protein, which is a component of the FA core complex 
      monoubiquitinating FANCD2, was required for this event. Furthermore, FANCD2 
      repression enhanced cell death upon AICAR treatments in transformed fibroblasts 
      and cell cycle arrest in the renal cell carcinoma cell line Caki-1. Overall, this 
      study showed FANCD2 involvement in response to AICAR, a chemical modulating 
      cellular energy metabolism.
FAU - Chun, Min Jeong
AU  - Chun MJ
AD  - Cancer Cell and Molecular Biology Branch Research Institute National Cancer 
      Center Goyang Korea.
FAU - Choi, Hana
AU  - Choi H
AD  - Cancer Cell and Molecular Biology Branch Research Institute National Cancer 
      Center Goyang Korea.
FAU - Jun, Dong Wha
AU  - Jun DW
AD  - Precision Medicine Branch Research Institute National Cancer Center Goyang Korea.
FAU - Kim, Sunshin
AU  - Kim S
AD  - Precision Medicine Branch Research Institute National Cancer Center Goyang Korea.
FAU - Kim, Yong-Nyun
AU  - Kim YN
AD  - Comparative Biomedicine Research Branch Research Institute National Cancer Center 
      Goyang Korea.
FAU - Kim, Soo-Youl
AU  - Kim SY
AD  - Cancer Cell and Molecular Biology Branch Research Institute National Cancer 
      Center Goyang Korea.
FAU - Lee, Chang-Hun
AU  - Lee CH
AUID- ORCID: 0000-0002-4083-2077
AD  - Cancer Cell and Molecular Biology Branch Research Institute National Cancer 
      Center Goyang Korea.
LA  - eng
PT  - Journal Article
DEP - 20170109
PL  - England
TA  - FEBS Open Bio
JT  - FEBS open bio
JID - 101580716
PMC - PMC5292659
OTO - NOTNLM
OT  - AICAR
OT  - AMP-activated protein kinase
OT  - FANCD2
EDAT- 2017/02/09 06:00
MHDA- 2017/02/09 06:01
PMCR- 2017/01/09
CRDT- 2017/02/09 06:00
PHST- 2016/10/27 00:00 [received]
PHST- 2016/12/14 00:00 [revised]
PHST- 2016/12/16 00:00 [accepted]
PHST- 2017/02/09 06:00 [entrez]
PHST- 2017/02/09 06:00 [pubmed]
PHST- 2017/02/09 06:01 [medline]
PHST- 2017/01/09 00:00 [pmc-release]
AID - FEB412185 [pii]
AID - 10.1002/2211-5463.12185 [doi]
PST - epublish
SO  - FEBS Open Bio. 2017 Jan 9;7(2):284-292. doi: 10.1002/2211-5463.12185. eCollection 
      2017 Feb.