Beyond Death: Unmasking the Intricacies of Apoptosis Escape.

Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to conditions such as cancer. Escape mechanisms include anoikis, mitochondrial DNA depletion, cellular FLICE inhibitory protein (c-FLIP), endosomal sorting complexes required for transport (ESCRT), mitotic slippage, anastasis, and blebbishield formation. Anoikis, triggered by cell detachment from the extracellular matrix, is pivotal in cancer research due to its role in cellular survival and metastasis. Mitochondrial DNA depletion, associated with cellular dysfunction and diseases such as breast and prostate cancer, links to apoptosis resistance. The c-FLIP protein family, notably CFLAR, regulates cell death processes as a truncated caspase-8 form. The ESCRT complex aids apoptosis evasion by repairing intracellular damage through increased Ca2+ levels. Antimitotic agents induce mitotic arrest in cancer treatment but can lead to mitotic slippage and tetraploid cell formation. Anastasis allows cells to resist apoptosis induced by various triggers. Blebbishield formation suppresses apoptosis indirectly in cancer stem cells by transforming apoptotic cells into blebbishields. In conclusion, the future of apoptosis research offers exciting possibilities for innovative therapeutic approaches, enhanced diagnostic tools, and a deeper understanding of the complex biological processes that govern cell fate. Collaborative efforts across disciplines, including molecular biology, genetics, immunology, and bioinformatics, will be essential to realize these prospects and improve patient outcomes in diverse disease contexts.

The Interrelationship Between FYN and miR-128/193a-5p/494 in Imatinib Resistance in Prostate Cancer.

BACKGROUND: C-KIT is a receptor tyrosine kinase with oncogenic properties overexpressed in PCa cases. Through the use of an alternative promoter, a truncated c-KIT protein (tr-KIT) of 30-50 kDa is generated, lacking the extracellular and transmembrane domain. Tr-KIT promotes the formation of a multi-molecular complex composed of Fyn, Plcγ1, and Sam68. Imatinib blocks the activity of full-length c-KIT but has no effect on tr-KIT. LNCaP is the human PCa cell line that shows tr-KIT overexpression and PC3 does not show tr-KIT overexpression. miR-128/193a- 5p/494 are miRNAs targeting FYN, PLCγ1, and SAM68 combinatorially. The study's question is: can miR-128/193a- 5p/494 be related to imatinib resistance in PCa? METHODS: LNCaP and PC3 cells were treated with imatinib in IC50 doses. Before and after imatinib administration, RNA was isolated and cDNA conversion was performed. By qPCR analysis, expression changes of tr-KIT specific pathway elements and miR-128/193a-5p/494 were analyzed before and after imatinib administration. RESULTS: After imatinib administration, miR-128/193a-5p/494 were significantly overexpressed in LNCaP cells while downregulated significantly in PC3 cells (p<0.05). Also, FYN was upregulated in LNCaP cells (p<0.05) but there was no change in PC3 after imatinib administration. CONCLUSION: Especially upregulation of FYN may sponge miR128/193a-5p/494 and downregulate their transcriptional activity in LNCaP cells having tr-KIT activity. So, miR-128/193a-5p/494 may have a critical role in imatinib resistance via a tr-KIT pathway.

Proteome analysis of the circadian clock protein PERIOD2.

Circadian rhythms are a series of endogenous autonomous 24-h oscillations generated by the circadian clock. At the molecular level, the circadian clock is based on a transcription-translation feedback loop, in which BMAL1 and CLOCK transcription factors of the positive arm activate the expression of CRYPTOCHROME (CRY) and PERIOD (PER) genes of the negative arm as well as the circadian clock-regulated genes. There are three PER proteins, of which PER2 shows the strongest oscillation at both stability and cellular localization level. Protein-protein interactions (PPIs) or interactome of the circadian clock proteins have been investigated using classical methods such as two-dimensional gel electrophoresis, immunoprecipitation-coupled mass spectrometry, and yeast-two hybrid assay where the dynamic and weak interactions are difficult to catch. To identify the interactome of PER2 we have adopted proximity-dependent labeling with biotin and mass spectrometry-based identification of labeled proteins (BioID). In addition to known interactions with such as CRY1 and CRY2, we have identified several new PPIs for PER2 and confirmed some of them using co-immunoprecipitation technique. This study characterizes the PER2 protein interactions in depth, and it also implies that using a fast BioID method with miniTurbo or TurboID coupled to other major circadian clock proteins might uncover other interactors in the clock that have yet to be discovered.