PMID- 26083323
OWN - NLM
STAT- MEDLINE
DCOM- 20160620
LR  - 20230815
IS  - 1554-8635 (Electronic)
IS  - 1554-8627 (Print)
IS  - 1554-8627 (Linking)
VI  - 11
IP  - 8
DP  - 2015
TI  - ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2 and 
      PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes during 
      hypoxia/reoxygenation.
PG  - 1308-25
LID - 10.1080/15548627.2015.1060386 [doi]
AB  - Recent studies have shown that the phosphorylation and dephosphorylation of ULK1 
      and ATG13 are related to autophagy activity. Although ATG16L1 is absolutely 
      required for autophagy induction by affecting the formation of autophagosomes, 
      the post-translational modification of ATG16L1 remains elusive. Here, we explored 
      the regulatory mechanism and role of ATG16L1 phosphorylation for autophagy 
      induction in cardiomyocytes. We showed that ATG16L1 was a phosphoprotein, because 
      phosphorylation of ATG16L1 was detected in rat cardiomyocytes during 
      hypoxia/reoxygenation (H/R). We not only demonstrated that CSNK2 (casein kinase 
      2) phosphorylated ATG16L1, but also identified the highly conserved Ser139 as the 
      critical phosphorylation residue for CSNK2. We further established that ATG16L1 
      associated with the ATG12-ATG5 complex in a Ser139 phosphorylation-dependent 
      manner. In agreement with this finding, CSNK2 inhibitor disrupted the 
      ATG12-ATG5-ATG16L1 complex. Importantly, phosphorylation of ATG16L1 on Ser139 was 
      responsible for H/R-induced autophagy in cardiomyocytes, which protects 
      cardiomyocytes from apoptosis. Conversely, we determined that wild-type PPP1 
      (protein phosphatase 1), but not the inactive mutant, associated with ATG16L1 and 
      antagonized CSNK2-mediated phosphorylation of ATG16L1. Interestingly, one RVxF 
      consensus site for PPP1 binding in the C-terminal tail of ATG16L1 was identified; 
      mutation of this site disrupted its association with ATG16L1. Notably, CSNK2 also 
      associated with PPP1, but ATG16L1 depletion impaired the interaction between 
      CSNK2 and PPP1. Collectively, these data identify ATG16L1 as a bona fide 
      physiological CSNK2 and PPP1 substrate, which reveals a novel molecular link from 
      CSNK2 to activation of the autophagy-specific ATG12-ATG5-ATG16L1 complex and 
      autophagy induction.
FAU - Song, Huiwen
AU  - Song H
AD  - a Department of Cardiology ; Affiliated Baoan Hospital of Southern Medical 
      University ; Shenzhen , China.
FAU - Pu, Jun
AU  - Pu J
FAU - Wang, Lin
AU  - Wang L
FAU - Wu, Lihua
AU  - Wu L
FAU - Xiao, Jianmin
AU  - Xiao J
FAU - Liu, Qigong
AU  - Liu Q
FAU - Chen, Jun
AU  - Chen J
FAU - Zhang, Min
AU  - Zhang M
FAU - Liu, Yang
AU  - Liu Y
FAU - Ni, Mingke
AU  - Ni M
FAU - Mo, Jinggang
AU  - Mo J
FAU - Zheng, Yunliang
AU  - Zheng Y
FAU - Wan, Deli
AU  - Wan D
FAU - Cai, XiongJiu
AU  - Cai X
FAU - Cao, Yaping
AU  - Cao Y
FAU - Xiao, Weiyi
AU  - Xiao W
FAU - Ye, Lei
AU  - Ye L
FAU - Tu, Enyuan
AU  - Tu E
FAU - Lin, Zhihai
AU  - Lin Z
FAU - Wen, Jianxin
AU  - Wen J
FAU - Lu, Xiaoling
AU  - Lu X
FAU - He, Jian
AU  - He J
FAU - Peng, Yi
AU  - Peng Y
FAU - Su, Jing
AU  - Su J
FAU - Zhang, Heng
AU  - Zhang H
FAU - Zhao, Yongxiang
AU  - Zhao Y
FAU - Lin, Meihua
AU  - Lin M
FAU - Zhang, Zhiyong
AU  - Zhang Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - 0 (ATG16L1 protein, human)
RN  - 0 (ATG5 protein, human)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (CSNK2A1 protein, human)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 3.1.3.16 (PPP1CA protein, human)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis
MH  - Autophagy
MH  - Autophagy-Related Protein 5
MH  - Autophagy-Related Proteins
MH  - Binding Sites
MH  - Carrier Proteins/*metabolism
MH  - Casein Kinase II/metabolism
MH  - Cell Hypoxia
MH  - Cell Lineage
MH  - *Gene Expression Regulation
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microtubule-Associated Proteins/metabolism
MH  - Molecular Sequence Data
MH  - Myocytes, Cardiac/*cytology
MH  - Oxygen/chemistry
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Phosphatase 1/*metabolism
MH  - Protein Structure, Tertiary
MH  - Recombinant Proteins/metabolism
MH  - Reperfusion Injury
MH  - Sequence Homology, Amino Acid
MH  - Serine/chemistry
PMC - PMC4590681
OTO - NOTNLM
OT  - ATG16L1
OT  - autophagy
OT  - cardiomyocyte
OT  - casein kinase 2
OT  - protein phosphatase 1
EDAT- 2015/06/18 06:00
MHDA- 2016/06/21 06:00
PMCR- 2016/09/14
CRDT- 2015/06/18 06:00
PHST- 2015/06/18 06:00 [entrez]
PHST- 2015/06/18 06:00 [pubmed]
PHST- 2016/06/21 06:00 [medline]
PHST- 2016/09/14 00:00 [pmc-release]
AID - 1060386 [pii]
AID - 10.1080/15548627.2015.1060386 [doi]
PST - ppublish
SO  - Autophagy. 2015;11(8):1308-25. doi: 10.1080/15548627.2015.1060386.