PMID- 28978663
OWN - NLM
STAT- MEDLINE
DCOM- 20171212
LR  - 20181202
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Linking)
VI  - 102
IP  - 6
DP  - 2017 Dec
TI  - Distinct TP73-DAPK2-ATG5 pathway involvement in ATO-mediated cell death versus 
      ATRA-mediated autophagy responses in APL.
PG  - 1357-1370
LID - 10.1189/jlb.1A0317-132R [doi]
AB  - We have previously demonstrated that the death-associated protein kinase 2 
      (DAPK2) expression is significantly reduced in acute myeloid leukemia (AML), 
      particularly in acute promyelocytic leukemia (APL) blast cells. In this study, we 
      aimed at further understanding DAPK2 function and regulation during arsenic 
      trioxide (ATO) cytotoxic or all-trans retinoic acid (ATRA) differentiation 
      therapy in APL cells. We found that the p53 family member transactivation 
      domain-p73 isoform (TAp73) binds to and activates the DAPK2 promoter, whereas the 
      dominant-negative DeltaNp73 isoform inhibits DAPK2 transcription. Furthermore, the 
      knocking down of tumor protein p73 (TP73) in NB4 cells resulted in reduced DAPK2 
      expression associated with decreased cell death and autophagy upon ATO and ATRA 
      treatment, respectively. Moreover, the silencing of DAPK2 revealed that DAPK2 is 
      an important downstream effector of p73 in ATO-induced apoptosis but not 
      autophagy responses of APL cells. In contrast, the p73-DAPK2 pathway is essential 
      for ATRA-induced autophagy that is mediated by an interaction of DAPK2 with the 
      key autophagy-related protein (ATG)5. Lastly, we show that DAPK2 binds and 
      stabilizes the p73 protein; thus, we propose a novel mechanism by which ATO- or 
      ATRA-induced therapy responses initiate a positive p73-DAPK2 feedback loop.
CI  - (c) Society for Leukocyte Biology.
FAU - Humbert, Magali
AU  - Humbert M
AD  - Division of Experimental Pathology, Institute of Pathology, University of Bern, 
      Switzerland; and magali.humbert@pathology.unibe.ch.
FAU - Federzoni, Elena A
AU  - Federzoni EA
AD  - Division of Experimental Pathology, Institute of Pathology, University of Bern, 
      Switzerland; and.
FAU - Tschan, Mario P
AU  - Tschan MP
AD  - Division of Experimental Pathology, Institute of Pathology, University of Bern, 
      Switzerland; and.
AD  - Graduate School for Cellular and Biomedical Sciences, University of Bern, 
      Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20171004
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Arsenicals)
RN  - 0 (Autophagy-Related Protein 12)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (Oxides)
RN  - 0 (Protein Isoforms)
RN  - 0 (Tumor Protein p73)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.11.1 (DAPK2 protein, human)
RN  - EC 2.7.11.1 (Death-Associated Protein Kinases)
RN  - S7V92P67HO (Arsenic Trioxide)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Arsenic Trioxide
MH  - Arsenicals/*pharmacology/therapeutic use
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Protein 12/metabolism
MH  - Autophagy-Related Protein 5/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Nucleus/drug effects/metabolism
MH  - Death-Associated Protein Kinases/genetics/*metabolism
MH  - Gene Knockdown Techniques
MH  - HEK293 Cells
MH  - Humans
MH  - Leukemia, Promyelocytic, Acute/drug therapy/genetics/*pathology
MH  - Models, Biological
MH  - Oxides/*pharmacology/therapeutic use
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding/drug effects
MH  - Protein Isoforms/metabolism
MH  - Protein Stability/drug effects
MH  - Signal Transduction/drug effects
MH  - Transcription, Genetic/drug effects
MH  - Tretinoin/*pharmacology/therapeutic use
MH  - Tumor Protein p73/*metabolism
OTO - NOTNLM
OT  - AML
OT  - DRP-1
OT  - apoptosis
OT  - p73
EDAT- 2017/10/06 06:00
MHDA- 2017/12/13 06:00
CRDT- 2017/10/06 06:00
PHST- 2017/03/31 00:00 [received]
PHST- 2017/08/18 00:00 [revised]
PHST- 2017/09/11 00:00 [accepted]
PHST- 2017/10/06 06:00 [pubmed]
PHST- 2017/12/13 06:00 [medline]
PHST- 2017/10/06 06:00 [entrez]
AID - jlb.1A0317-132R [pii]
AID - 10.1189/jlb.1A0317-132R [doi]
PST - ppublish
SO  - J Leukoc Biol. 2017 Dec;102(6):1357-1370. doi: 10.1189/jlb.1A0317-132R. Epub 2017 
      Oct 4.