生命科学科研大百科

This article elaborates on the activation mechanism, phosphorylation modification of key proteins and transcriptional regulation of the NF-κB signaling pathway. In the cytoplasm, NF-κB remains inactive by binding to inhibitory IκB proteins. The IKK complex phosphorylates IκBα, IκBβ and IκBε, triggering their ubiquitination and proteasomal degradation. The liberated NF-κB dimers then translocate into the nucleus to execute transcriptional functions. The mammalian NF-κB family consists of five members: p65/RelA, c-Rel, RelB, NF-κB1 and NF-κB2. After proteolytic processing, precursor proteins form dimers with Rel proteins to bind DNA. Multiple phosphorylation sites modulate the transcriptional activity of p65. This paper also lists commercial antibodies for research on this pathway with their species reactivity and applicable experimental techniques, along with relevant references, providing a reference for basic research and experimental detection of the NF-κB pathway.

The nuclear factor κB (NF-κB) family participates extensively in inflammatory and immune responses. Distinct from the canonical NF-κB pathway activated by TNFα and LPS, the non-canonical pathway is triggered by BAFF, CD40L and other stimuli. This pathway relies on NF-κB-inducing kinase (NIK) and IKKα to mediate the phosphorylation and partial proteasomal degradation of NF-κB2 p100 into active p52. TRAF2 and TRAF3 act as negative regulators in this process. The non-canonical NF-κB pathway is essential for B cell maturation, the formation of peripheral lymphoid tissues and the prevention of autoimmune diseases. This article also lists a series of specific antibodies for related protein detection, along with relevant research references.

TRAFs (TNF receptor-associated factors) are a family of multifunctional adaptor proteins that bind to surface receptors and recruit additional proteins to form multiprotein signaling complexes capable of promoting cellular responses. Members of the TRAF family share a common carboxy-terminal "TRAF domain", which mediates interactions with associated proteins; many also contain amino-terminal Zinc/RING finger motifs. The first TRAFs identified, TRAF1 and TRAF2, were found by virtue of their interactions with the cytoplasmic domain of TNF-receptor 2 (TNFRII). The six known TRAFs (TRAF1-6) act as adaptor proteins for a wide range of cell surface receptors and participate in the regulation of cell survival, proliferation, differentiation, and stress responses.

Traumatic brain injury (TBI) is a worldwide health issue that significantly affects the patient as well as their family. Annual total cost of nonfatal TBI in 2016 was $40.6 billion in the United States. In addition to acute brain injury, even mild cases, can lead to cognitive impairment and long-term psychiatric changes. More long term, TBI patients exhibit lower resilience to neurodegenerative disease-associated pathology. Treatment of TBI is made more difficult due to lack of reliable biomarkers to detect TBI. Several proteins are of interest, which are candidates for measurement in blood after TBI. Glial fibrillary acidic protein (GFAP) is an astrocytic intermediate filament protein. As a cytoskeletal protein, GFAP helps provide structural support to astrocytes, which provide metabolic support to neurons and maintains the blood brain barrier. The number and size of astrocytes, in a process called astrogliosis, is also positively correlated with brain injury. Also abundantly expressed in astrocytes, S100B is commonly used as an astrocytic marker and is positively correlated with TBI. Neurofilament-L (NfL) and tau are part of the neuronal cytoskeleton that provide structure to axons. Axons are covered by a multi-layered membrane called the myelin sheath. Myelin basic protein (MBP) is enriched in myelin and helps maintain its structure. UCHL1 and Enolase-2 are ubiquitin hydrolases and glycolytic enzymes, respectively, that are enriched in neurons. PSD95 is an adaptor protein enriched at postsynaptic sites in neurons. After brain injury, neuron-enriched proteins, as well as proteins that maintain neuronal/axonal integrity, can be measured in the blood, reflecting neuronal damage.

The tricarboxylic acid (TCA) cycle includes various enzymatic reactions that constitute a key part of cellular aerobic respiration. The transport of the glycolytic end product pyruvate into mitochondria and the decarboxylation of pyruvate in the TCA cycle generate energy through oxidative phosphorylation under aerobic conditions. Two inner mitochondrial membrane proteins, mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2), form a 150 kDa complex and are essential proteins in the facilitated transport of pyruvate into mitochondria . Citrate synthase catalyzes the first and rate-limiting reaction of the TCA cycle. Mitochondrial aconitase 2 (ACO2) catalyzes the conversion of citrate to isocitrate via cis-aconitate. IDH1 and IDH2 are two of the three isocitrate dehydrogenases that catalyze oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). IDH1 functions as a tumor suppressor in the cytoplasm and peroxisomes, whereas IDH2 is in mitochondria and is involved in the TCA cycle. Mutations in IDH2 have also been identified in malignant gliomas. Dihydrolipoamide succinyltransferase (DLST) is a subunit of the α-ketoglutarate dehydrogenase complex, a key enzymatic complex in the TCA cycle. Succinate dehydrogenase subunit A (SDHA) is a component of the TCA cycle and the electron transport chain and is involved in the oxidation of succinate. Fumarase catalyzes the conversion of fumarate to malate. Fumarase deficiency leads to the accumulation of fumarate, an oncometabolite that has been shown to promote epithelial-to-mesenchymal-transition (EMT), a developmental process that has been implicated in oncogenesis.

NF-κB/Rel family is a key transcription factor regulating inflammation and immune responses. Mammals have five members. NF-κB is inhibited by IκB in resting cells and translocates into nucleus after activation. Relevant antibodies and references are also listed.

Pericytes are key components of the blood-brain barrier (BBB), closely interacting with endothelial cells (ECs) via signaling pathways like PDGF-β. Major pericyte markers include PDGFR-β, α-smooth muscle actin, desmin, CD146, CD13, CD31, and NG2. These markers regulate pericyte-EC communication, cytoskeleton function, and inflammatory responses in the central nervous system.

Platelet-derived growth factor (PDGF) forms dimers that bind PDGF receptors, activating downstream signaling molecules such as PI3K, SHP-2, Akt, and Erk1/2. These pathways regulate cell growth, migration, and differentiation. PDGF signaling is frequently dysregulated in solid tumors, supporting tumor cell proliferation, stromal interaction, and angiogenesis. Targeting PDGF signaling represents a potential therapeutic strategy for cancer.

Parthanatos is a regulated cell death triggered by poly(ADP-ribose) (PAR) accumulation, driven by overactivated PARP-1. Excessive PAR binds AIF, which complexes with MIF, translocates to the nucleus, and cleaves DNA, causing cell death. It is closely linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s.

This text introduces common immunohistochemical markers for pancreatic cells and tumors. Insulin/C‑peptide, glucagon, and NKX6.1 serve as key markers for pancreatic β and α cells, respectively. Pan‑keratin and CD200 help differentiate pancreatic adenocarcinomas and neuroendocrine tumors. Relevant antibodies and their applications are also listed.