PMID- 30847993
OWN - NLM
STAT- MEDLINE
DCOM- 20190617
LR  - 20210109
IS  - 1365-2184 (Electronic)
IS  - 0960-7722 (Print)
IS  - 0960-7722 (Linking)
VI  - 52
IP  - 3
DP  - 2019 May
TI  - Lic regulates JNK-mediated cell death in Drosophila.
PG  - e12593
LID - 10.1111/cpr.12593 [doi]
LID - e12593
AB  - OBJECTIVES: The evolutionary conserved JNK pathway plays crucial role in cell 
      death, yet factors that modulate this signalling have not been fully disclosed. 
      In this study, we aim to identify additional factors that regulate JNK signalling 
      in cell death, and characterize the underlying mechanisms. MATERIALS AND METHODS: 
      Drosophila were raised on standard media, and cross was carried out at 25 degrees C. The 
      Gal4/UAS system was used to express proteins or RNAi in a specific temporal and 
      spatial pattern. Gene expression was revealed by GFP fluorescence, X-gal staining 
      or immunostaining of 3rd instar larval eye and wing discs. Cell death was 
      visualized by acridine orange (AO) staining. Images of fly eyes and wings were 
      taken by OLYMPUS microscopes. RESULTS: We found that licorne (lic) encoding the 
      Drosophila MKK3 is an essential regulator of JNK-mediated cell death. Firstly, 
      loss of lic suppressed ectopic Egr-triggered JNK activation and cell death in eye 
      and wing development. Secondary, lic is necessary for loss-of-cell 
      polarity-induced, physiological JNK-dependent cell death in wing development. 
      Thirdly, Lic overexpression is sufficient to initiate JNK-mediated cell death in 
      developing eyes and wings. Furthermore, ectopic Lic activates JNK signalling by 
      promoting JNK phosphorylation. Finally, genetic epistatic analysis confirmed that 
      Lic acts in parallel with Hep in the Egr-JNK pathway. CONCLUSIONS: This study not 
      only identified Lic as a novel component of the JNK signalling, but also 
      disclosed the crucial roles and mechanism of Lic in cell death.
CI  - (c) 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.
FAU - Sun, Yihao
AU  - Sun Y
AUID- ORCID: 0000-0002-5829-8554
AD  - The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of 
      Signaling and Diseases Research, School of Life Science and Technology, Tongji 
      University, Shanghai, China.
FAU - Zhang, Di
AU  - Zhang D
AD  - The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of 
      Signaling and Diseases Research, School of Life Science and Technology, Tongji 
      University, Shanghai, China.
FAU - Li, Chenglin
AU  - Li C
AD  - The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of 
      Signaling and Diseases Research, School of Life Science and Technology, Tongji 
      University, Shanghai, China.
FAU - Huang, Jiuhong
AU  - Huang J
AD  - International Academy of Targeted Therapeutics and Innovation, Chongqing 
      University of Arts and Sciences, Chongqing, China.
FAU - Li, Wenzhe
AU  - Li W
AD  - The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of 
      Signaling and Diseases Research, School of Life Science and Technology, Tongji 
      University, Shanghai, China.
FAU - Qiu, Yu
AU  - Qiu Y
AD  - The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of 
      Signaling and Diseases Research, School of Life Science and Technology, Tongji 
      University, Shanghai, China.
FAU - Mao, Aiwu
AU  - Mao A
AD  - Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 
      China.
FAU - Zhou, Mingcheng
AU  - Zhou M
AD  - The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of 
      Signaling and Diseases Research, School of Life Science and Technology, Tongji 
      University, Shanghai, China.
FAU - Xue, Lei
AU  - Xue L
AUID- ORCID: 0000-0001-6947-8414
AD  - The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of 
      Signaling and Diseases Research, School of Life Science and Technology, Tongji 
      University, Shanghai, China.
LA  - eng
GR  - 31571516/National Natural Science Foundation of China/
GR  - 31771595/National Natural Science Foundation of China/
GR  - 09DZ2260100/Shanghai Committee of Science and Technology/
GR  - 18140900400/Shanghai Committee of Science and Technology/
GR  - 18430711600/Shanghai Committee of Science and Technology/
PT  - Journal Article
DEP - 20190307
PL  - England
TA  - Cell Prolif
JT  - Cell proliferation
JID - 9105195
RN  - 0 (Drosophila Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (egr protein, Drosophila)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (lic protein, Drosophila)
RN  - EC 2.7.12.2 (Hep protein, Drosophila)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - *Cell Death/genetics
MH  - Drosophila Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Drosophila melanogaster/*cytology/genetics/*metabolism
MH  - Epistasis, Genetic
MH  - Eye/growth & development/metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Genes, Insect
MH  - *MAP Kinase Signaling System/genetics
MH  - Membrane Proteins/genetics
MH  - Mitogen-Activated Protein Kinase Kinases/genetics
MH  - Protein Kinases/genetics/*metabolism
MH  - RNA Interference
MH  - Wings, Animal/growth & development/metabolism
PMC - PMC6536442
OTO - NOTNLM
OT  - Egr
OT  - JNK
OT  - Lic
OT  - MKK3
OT  - cell death
COIS- The authors declare no conflict of interest.
EDAT- 2019/03/09 06:00
MHDA- 2019/06/18 06:00
PMCR- 2019/03/07
CRDT- 2019/03/09 06:00
PHST- 2018/10/16 00:00 [received]
PHST- 2019/01/30 00:00 [revised]
PHST- 2019/01/31 00:00 [accepted]
PHST- 2019/03/09 06:00 [pubmed]
PHST- 2019/06/18 06:00 [medline]
PHST- 2019/03/09 06:00 [entrez]
PHST- 2019/03/07 00:00 [pmc-release]
AID - CPR12593 [pii]
AID - 10.1111/cpr.12593 [doi]
PST - ppublish
SO  - Cell Prolif. 2019 May;52(3):e12593. doi: 10.1111/cpr.12593. Epub 2019 Mar 7.