Редактирование: DAPK1

Death-associated protein kinase 1 (EC 2.7.11.1) (DAP kinase 1) [DAPK]

==Publications==

{{medline-entry
|title=SerThr-PhosphoProteome of Brain from Aged [[PINK1]]-KO A53T-[[SNCA]] Mice Reveals pT1928-[[MAP1B]] and pS3781-[[ANK2]] Deficits, as Hub between Autophagy and Synapse Changes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31277379
|abstract=Hereditary Parkinson's disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein ([[SNCA]]) as stressor or the autosomal recessive deficiency of [[PINK1]] Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of [[PINK1]]-knockout with overexpression of [[SNCA]]  in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As an exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in [[MAP1B]], a microtubule-associated protein, and a similar reduction of phosphoSer3781 in [[ANK2]], an interactor of microtubules. [[MAP1B]] depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension, and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was also detected for other microtubule and microfilament factors, namely [[MAP2]] , [[MARK1]] , [[MAP1A]] , [[KIF1A]] , 4.1N , 4.1G , and [[ADD2]] . While the [[MAP1B]] heavy chain supports regeneration and growth cones, its light chain assists [[DAPK1]]-mediated autophagy. Interestingly, relevant phosphorylation decreases of [[DAPK2]] , [[VPS13D]] , and [[VPS13C]]  in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM [[C2]] domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of [[ANK2]]/[[MAP1B]] expression on [[PINK1]] levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that [[MAP1B]]/[[ANK2]] phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in [i]Drosophila melanogaster[/i] that the [[MAP1B]] ortholog futsch in the presynapse is a primary target of the PARK8 protein [[LRRK2]], and on a report that [[MAP1B]] is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, [i][[ANK2]][/i] gene locus variants are associated with the risk of PD, [[ANK2]] interacts with [[PINK1]]/Parkin-target proteins such as MIRO1 or [[ATP1A2]], and [[ANK2]]-derived peptides are potent inhibitors of autophagy.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Ankyrins
* Autophagy
* Brain
* Mice, Knockout
* Mice, Mutant Strains
* Microtubule-Associated Proteins
* Microtubules
* Phosphoproteins
* Phosphorylation
* Phosphoserine
* Phosphothreonine
* Protein Domains
* Protein Kinases
* Proteome
* Synapses
* alpha-Synuclein
|keywords=* PINK1
* Parkinson’s disease
* alpha-synuclein
* autophagy
* brain phosphorylome
* microtubular cytoskeleton
* synaptic signaling
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651490
}}
{{medline-entry
|title=Degradation of Caytaxin Causes Learning and Memory Deficits via Activation of [[DAPK1]] in Aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30120735
|abstract=Loss of memory is an inevitable clinic sign in aging, but its underlying mechanisms remain unclear. Here we show that death-associated protein kinase ([[DAPK1]]) is involved in the decays of learning and memory in aging via degradation of Caytaxin, a brain-specific member of BNIP-2. [[DAPK1]] becomes activated in the hippocampus of mice during aging. Activation of [[DAPK1]] is closely associated with degradation of Caytaxin protein. Silencing Caytaxin by the expression of small interfering RNA (siRNA) that targets specifically to Caytaxin in the hippocampus of adult mice impairs the learning and memory. Genetic inactivation of [[DAPK1]] by deletion of [[DAPK1]] kinase domain prevents the degradation of Caytaxin and protects against learning and memory declines. Thus, activation of [[DAPK1]] impairs learning and memory by degrading Caytaxin during aging.
|mesh-terms=* Aging
* Animals
* Caspase 3
* Death-Associated Protein Kinases
* Enzyme Activation
* Gene Silencing
* Male
* Memory
* Memory Disorders
* Mice, Inbred C57BL
* Nerve Tissue Proteins
* Neurons
* Proteolysis
|keywords=* Aging
* Caytaxin
* DAPK1
* Learning and memory
|full-text-url=https://sci-hub.do/10.1007/s12035-018-1312-5
}}
{{medline-entry
|title=Differential expression of senescence and cell death factors in non-small cell lung and colorectal tumors showing telomere attrition.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22433385
|abstract=The main aim of this work is to investigate the expression of factors related to senescence and cell death pathways in non-small cell lung cancers (NSCLCs) and colorectal cancers (CRCs) in relation to telomere status. We analyzed 158 tissue samples, 36 NSCLCs, 43 CRCs, and their corresponding control tissues obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. Expression of factors related to senescence, cell death pathways, transformation and tumorigenesis was investigated using arrays. Results were validated by real-time quantitative PCR. Considering tumors with telomere shortening, expression for [[BNIP3]], [[DAPK1]], [[NDRG1]], [[EGFR]], and [[[[CDKN2A]]]] was significantly higher in NSCLC than in CRC, whereas [[TP53]] was overexpressed in CRC with respect to NSCLC. Moreover, compared to nontumor samples, [[DAPK1]], [[GADD45A]], [[SHC1]], and [[TP53]] were downregulated in the group of NSCLCs with telomere shortening, and no significant differences were found in CRC. In NSCLC, the failure of pathways which involve factors such as [[DAPK1]], [[GADD45A]], [[SHC1]], and [[TP53]], in response to short telomeres, could promote tumor progression. In CRC, the viability of these pathways in response to short telomeres could contribute to limiting tumorigenesis.
|mesh-terms=* Adenocarcinoma
* Aged
* Aging
* Biomarkers, Tumor
* Carcinoma, Large Cell
* Carcinoma, Non-Small-Cell Lung
* Carcinoma, Squamous Cell
* Cell Death
* Colon
* Colorectal Neoplasms
* Female
* Gene Expression Profiling
* Humans
* Lung
* Lung Neoplasms
* Male
* Oligonucleotide Array Sequence Analysis
* Prognosis
* Rectum
* Telomerase
* Telomere
* Telomere Shortening

|full-text-url=https://sci-hub.do/10.1159/000335678
}}