Organelle interactions occur among multiple organelles, including the endoplasmic reticulum (ER), mitochondria, Golgi apparatus, peroxisomes, lipid droplets (LDs), endosomes, and lysosomes. Imbalanced organelle interactions may contribute to various pathological processes. Increasing evidence indicates that abnormal organelle communication promotes cellular senescence and is associated with organ aging.
Axl, Mer and Tyro3 are three members of the TAM family receptor tyrosine kinase that share a common NCAM (neural adhesion molecule)-related extracellular domain and a conserved intracellular tyrosine kinase domain. These receptors bind common homologous vitamin K dependent protein GAS6 and protein S to activate downstream signaling pathways. TAM family receptors are involved in the development of immune, nervous, vascular and reproductive systems, autoimmune disease, cancer drug resistance and tumor immunity response. Axl (Tyr698), Axl (Tyr702), Mer Tyr(749) and Tyro3 (Tyr681) are conserved autophosphorylation sites located in the activation loop of the respective tyrosine kinase domains. Phosphorylation at these sites is required for full kinase activation of each of the corresponding receptors.
Exposure to ultraviolet radiation (UV) has a profound impact on human health and disease. Low level UV exposure induces the production of vitamin D and is a key regulator of calcium metabolism. Conversely, overexposure to UV is associated with an increased risk of cancer, immunosuppression, and many eye disorders, such as cataracts. Photons of UV light can directly damage DNA causing thymine dimers and other pyrimidine dimers between adjacent bases. Free radicals and reactive oxygen species induced by UV exposure also result in DNA lesions and have been linked to malignant melanoma. DNA damage from replicative stress and genotoxic agents like UV activate the ATR-mediated checkpoint pathway and stimulate DNA repair, cell cycle arrest, and apoptosis. ATR recruitment to sites of DNA damage and activation depends, at least in part, on interaction with the complex of single-stranded DNA, Replication Protein A (RPA), and direct binding to the ATR-associated adapter protein, ATRIP. In addition, the Rad17-RFC and Rad9-Rad1-Hus1 protein complexes are independently recruited with TopBP1 to fully activate the checkpoint response . BRIT1 (MCPH1) is required for UV-induced formation of ATR, RPA, and p-Rad17 foci at sites of DNA damage and may regulate the expression of several DNA damage response proteins. Once activated, ATR phosphorylates a number of mediators, including histone H2AX Ser139 and Chk1 kinase at Ser345. H2AX phosphorylation is a marker of DNA damage. Complete loss of H2AX results in reduced Chk1 activation and impaired survival of cells after UV exposure . Chk1 and Chk2 kinase activation is essential for checkpoint-mediated control of cell cycle progression. Checkpoint kinases stimulate cell cycle arrest by phosphorylation of a group of tyrosine phosphatases known as Cdc25A, Cdc25B, and Cdc25C. Both Chk1 and Chk2 kinases phosphorylate Cdc25C at Ser216, which promotes binding to 14-3-3 proteins and subsequent nuclear export of Cdc25C . This prevents Cdc25C from activating the Cdc2/cyclin B complex, which is required for entry into mitosis.
NETosis is a regulated cell death process in neutrophils, characterized by the release of chromatin web-like structures known as neutrophil extracellular traps (NETs). It plays critical roles in host defense against pathogens and is implicated in various diseases, including autoimmunity, thrombosis, and cancer. Key molecular drivers include the calcium-dependent enzyme PAD4, which mediates histone hypercitrullination, and proteases such as neutrophil elastase (ELANE), myeloperoxidase (MPO), and Cathepsin G, which promote chromatin decondensation and cytoskeletal disruption. This overview highlights the core mechanisms of NETosis and lists relevant antibodies for detecting key NETosis-related proteins.
Necroptosis is a regulated form of necrotic cell death triggered by inflammatory signals such as TNF cytokines, TLRs, and ischemic injury. It is initiated by the necrosome complex containing RIP and RIP3 kinases and is negatively regulated by caspases. Key phosphorylation events include RIP1 at Ser14/15/161/166 and RIP3 at Ser227, leading to MLKL phosphorylation at Thr357 and Ser358. Phosphorylated MLKL oligomerizes and translocates to the plasma membrane, compromising membrane integrity. This pathway is specifically inhibited by necrostatin-1 (Nec-1).
N6-methyladenosine (m6A) is a common RNA modification recognized by YTH domain-containing proteins, including YTHDC1, YTHDC2, YTHDF1, YTHDF2, and YTHDF3. YTHDC1 regulates alternative splicing, while YTHDC2 enhances translation efficiency. Among YTHDF family members, YTHDF1 promotes mRNA translation, YTHDF2 facilitates mRNA degradation, and YTHDF3 acts as an auxiliary protein. These m6A binding proteins play key roles in mRNA metabolism and disease progression.
The Myc/Max/Mad network regulates cell proliferation, differentiation, and apoptosis through bHLH-ZIP domain-mediated dimerization and DNA binding. Max serves as a central hub, forming homodimers or heterodimers with Myc and Mad families, which exert opposing transcriptional effects. The Myc family (c-Myc, N-Myc, L-Myc) shows distinct expression and amplification patterns in cancers, including mutually exclusive amplifications in neuroblastoma (N-Myc) and small cell lung cancer (L-Myc). Phosphorylation of c-Myc at Ser62 and Thr58 controls its proteasomal degradation. Key antibodies and references are also summarized.
The cytoskeleton consists of three types of cytosolic fibers: microfilaments (actin filaments), intermediate filaments, and microtubules. Major types of intermediate filaments are distinguished by their cell-specific expression: cytokeratins (epithelial cells), glial fibrillary acidic protein (GFAP) (glial cells), desmin (skeletal, visceral, and certain vascular smooth muscle cells), vimentin (mesenchyme origin), and neurofilaments (neurons).
The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that acts as a sensor of ATP and amino acids, coordinating nutrient availability and cell growth. Activated mTOR promotes the phosphorylation of p70 S6 kinase and inactivates 4E-BP1 through the PI3K/Akt signaling pathway, thereby regulating specific mRNA translation. mTOR forms two distinct complexes, mTORC1 (bound to Raptor) and mTORC2 (bound to Rictor and GβL), which mediate different downstream signaling events. Rapamycin inhibits mTORC1 activity by disrupting the mTOR–Raptor interaction. Abnormal regulation of mTOR is closely associated with tumorigenesis and ocular neurodegenerative diseases, making it a promising therapeutic target. This paper reviews the core molecular mechanisms of the mTOR signaling pathway and its relevance to retinal neurodegeneration, providing a theoretical basis for targeted antibody development and disease intervention.
The mammalian Mediator complex is a multi-subunit protein complex that relays signals from transcription factors to RNA polymerase II (Pol II) and the basal transcription machinery, acting as a centralized hub and integrator for transcriptional regulation. It participates in epigenetic regulation, transcriptional elongation, transcription termination, mRNA processing, non-coding RNA activation, and super-enhancer formation, thereby regulating insulin signaling, NF-κB-dependent signaling, stem cell pluripotency and self-renewal, colon cancer cell proliferation and other key biological processes. The mammalian Mediator complex consists of 31 protein subunits and can be divided into four structural modules: head, middle, tail, and CDK8 kinase module. The CDK8 kinase module acts as a molecular switch, phosphorylating the C-terminal domain of Rpb1, the large subunit of RNA polymerase II, to inhibit the recruitment and transcription initiation of RNA polymerase II.
