Редактирование: BAK1

Bcl-2 homologous antagonist/killer (Apoptosis regulator BAK) (Bcl-2-like protein 7) (Bcl2-L-7) [BAK] [BCL2L7] [CDN1]

==Publications==

{{medline-entry
|title=Developmental Attenuation of Neuronal Apoptosis by Neural-Specific Splicing of Bak1 Microexon.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32710818
|abstract=Continuous neuronal survival is vital for mammals because mammalian brains have limited regeneration capability. After neurogenesis, suppression of apoptosis is needed to ensure a neuron's long-term survival. Here we describe a robust genetic program that intrinsically attenuates apoptosis competence in neurons. Developmental downregulation of the splicing regulator [[PTBP1]] in immature neurons allows neural-specific splicing of the evolutionarily conserved Bak1 microexon 5. Exon 5 inclusion triggers nonsense-mediated mRNA decay (NMD) and unproductive translation of Bak1 transcripts (N-Bak mRNA), leading to suppression of pro-apoptotic [[BAK1]] proteins and allowing neurons to reduce apoptosis. Germline heterozygous ablation of exon 5 increases [[BAK1]] proteins exclusively in the brain, inflates neuronal apoptosis, and leads to early postnatal mortality. Therefore, neural-specific exon 5 splicing and depletion of [[BAK1]] proteins uniquely repress neuronal apoptosis. Although apoptosis is important for development, attenuation of apoptosis competence through neural-specific splicing of the Bak1 microexon is essential for neuronal and animal survival.
|mesh-terms=* Animals
* Apoptosis
* Brain
* Cell Line, Tumor
* Cells, Cultured
* Female
* Heterogeneous-Nuclear Ribonucleoproteins
* Male
* Mice
* Mice, Inbred C57BL
* Mutation
* Neural Stem Cells
* Neurogenesis
* Nonsense Mediated mRNA Decay
* Polypyrimidine Tract-Binding Protein
* RNA Splicing
* bcl-2 Homologous Antagonist-Killer Protein
|keywords=* AS-NMD
* BAK
* BCL2 family proteins
* NMD
* PTB
* PTBP
* PTBP2
* UPF2
* alternative splicing
* cell death
* neural development
* neurogenesis
* neuronal lifespan
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529960
}}
{{medline-entry
|title=[[SIRT6]] histone deacetylase functions as a potential oncogene in human melanoma.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29234488
|abstract=Melanoma is an aggressive skin cancer that can rapidly metastasize to become fatal, if not diagnosed early. Despite recent therapeutic advances, management of melanoma remains difficult. Therefore, novel molecular targets and strategies are required to manage this neoplasm. This study was undertaken to determine the role of the sirtuin [[SIRT6]] in melanoma. Employing a panel of human melanoma cells and normal human melanocytes, we found significant [[SIRT6]] mRNA and protein upregulation in melanoma cells. Further, using a tissue microarray coupled with quantitative Vectra analysis, we demonstrated significant [[SIRT6]] overexpression in human melanoma tissues. Lentiviral short hairpin RNA-mediated knockdown of [[SIRT6]] in A375 and Hs 294T human melanoma cells significantly decreased cell growth, viability, and colony formation, induced G1-phase arrest and increased senescence-associated beta-galactosidase staining. As autophagy is important in melanoma and is associated with [[SIRT6]], we used a qPCR array to study [[SIRT6]] knockdown in A375 cells. We found significant modulation in several genes and/or proteins (decreases in [[AKT1]], [[ATG12]], [[ATG3]], [[ATG7]], [[BAK1]], [[BCL2L1]], [[CLN3]], [[CTSB]], [[CTSS]], [[DRAM2]], [[HSP90AA1]], [[IRGM]], [[NPC1]], [[SQSTM1]], [[TNF]], and BECN1; increases in [[GAA]], ATG10). Our data suggests that increased [[SIRT6]] expression may contribute to melanoma development and/or progression, potentially via senescence-and autophagy-related pathways.

|keywords=* SIRT6
* autophagy
* melanoma
* senescence
* sirtuins
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724804
}}
{{medline-entry
|title=The dominant negative ARM domain uncovers multiple functions of PUB13 in Arabidopsis immunity, flowering, and senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25873653
|abstract=Regulating the intensity and duration of immune responses is crucial to combat infections without deleterious side effects. Arabidopsis FLS2, the receptor for bacterial flagellin, activates immune signalling by association with its partner [[BAK1]]. Upon flagellin (flg22) perception, the plant U-box E3 ubiquitin ligases PUB12 and PUB13 complex with FLS2 in a [[BAK1]]-dependent manner, and ubiquitinate FLS2 for protein degradation, thereby down-regulating flagellin signalling. Domain deletion analysis indicates that the ARM domain of PUB13 interacts with the FLS2-[[BAK1]] complex and is phosphorylated by [[BAK1]]. Overexpression of the PUB13 ARM domain alone inhibits flg22-induced FLS2-PUB13 association and PUB12/13-mediated FLS2 ubiquitination and degradation in Arabidopsis, suggesting that ectopic expression of the ARM domain in planta generates a dominant negative effect via blocking the ubiquitination activity. Similar to the pub12pub13 double mutant, transgenic plants expressing the PUB13 ARM domain display enhanced immune responses compared with wild-type plants. Moreover, PUB13ARM transgenic plants and the pub12pub13 mutant are more sensitive to stress-induced leaf senescence accompanied by elevated expression of stress-induced senescence marker genes. The resemblance between PUB13ARM transgenic plants and the pub12pub13 mutant provides genetic evidence that ectopic expression of the PUB ARM domain serves as an alternative approach to dissect the overlapping functions of closely related PUB genes. 
|mesh-terms=* Arabidopsis
* Arabidopsis Proteins
* Cellular Senescence
* Flagellin
* Flowers
* Host-Pathogen Interactions
* Mutation
* Phosphorylation
* Plant Immunity
* Plants, Genetically Modified
* Protein Kinases
* Protein Structure, Tertiary
* Proteolysis
* Ubiquitin-Protein Ligases
* Ubiquitination
|keywords=* Dominant negative
* flowering
* phosphorylation
* plant–microbe interactions
* receptors
* senescence
* ubiquitination.
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449551
}}