肿瘤坏死因子

肿瘤坏死因子（TNF）旧称肿瘤坏死因子-α（TNF-α）^[1]以区别肿瘤坏死因子-β，属肿瘤坏死因子超家族一员，是一种涉及到系统性炎症的细胞因子，同时也是属于引起急相反应（英语：Acute-phase protein）的众多细胞因子中的一员。主要由巨噬细胞分泌，不过有一些其它类型的细胞也能生产。

肿瘤坏死因子
PDB rendering based on 1TNF.
有效结构 PDB 直系同源检索：PDBe, RCSB PDB查询代码列表 1A8M​, 1TNF​, 2AZ5​, 2E7A​, 2TUN​, 2ZJC​, 2ZPX​, 3ALQ​, 3IT8​, 3L9J​, 4TSV​, 5TSW​
标识
代号	TNF; DIF; TNF-alpha; TNFA; TNFSF2
扩展标识	遗传学：191160 鼠基因：104798 同源基因：496 ChEMBL: 1825 GeneCards: TNF Gene
基因本体论描述 分子功能 · protease binding · cytokine activity · tumor necrosis factor receptor binding · protein binding · identical protein binding · transcription regulatory region DNA binding 细胞成分 · phagocytic cup · extracellular space · plasma membrane · integral to plasma membrane · external side of plasma membrane · cell surface · membrane raft · recycling endosome 生物过程 · protein import into nucleus, translocation · negative regulation of transcription from RNA polymerase II promoter · MAPK cascade · activation of MAPKKK activity · activation of MAPK activity · response to hypoxia · cell activation · positive regulation of cytokine production · positive regulation of protein phosphorylation · negative regulation of L-glutamate transport · chronic inflammatory response to antigenic stimulus · negative regulation of cytokine secretion involved in immune response · positive regulation of chronic inflammatory response to antigenic stimulus · positive regulation of humoral immune response mediated by circulating immunoglobulin · skeletal muscle contraction · glucose metabolic process · apoptotic process · anti-apoptosis · induction of apoptosis · activation of cysteine-type endopeptidase activity involved in apoptotic process · transformed cell apoptotic process · inflammatory response · humoral immune response · JNK cascade · negative regulation of cell proliferation · induction of apoptosis by extracellular signals · induction of apoptosis by extracellular signals · induction of apoptosis via death domain receptors · response to mechanical stimulus · response to virus · response to salt stress · organ morphogenesis · negative regulation of gene expression · negative regulation of alkaline phosphatase activity · negative regulation of lipid storage · positive regulation of necrotic cell death · response to activity · calcium-mediated signaling · extracellular matrix organization · sequestering of triglyceride · positive regulation of protein complex assembly · positive regulation of fever generation · lipopolysaccharide-mediated signaling pathway · negative regulation of interleukin-6 production · positive regulation of chemokine production · positive regulation of interferon-gamma production · positive regulation of interleukin-6 production · receptor biosynthetic process · positive regulation of peptidyl-serine phosphorylation · tumor necrosis factor-mediated signaling pathway · positive regulation of heterotypic cell-cell adhesion · positive regulation of NF-kappaB import into nucleus · response to drug · positive regulation of apoptotic process · positive regulation of apoptotic process · negative regulation of apoptotic process · positive regulation of programmed cell death · regulation of I-kappaB kinase/NF-kappaB cascade · positive regulation of I-kappaB kinase/NF-kappaB cascade · positive regulation of protein complex disassembly · positive regulation of MAP kinase activity · protein kinase B signaling cascade · positive regulation of neuron apoptotic process · negative regulation of growth of symbiont in host · negative regulation of viral genome replication · positive regulation of chemokine biosynthetic process · positive regulation of interleukin-8 biosynthetic process · positive regulation of nitric oxide biosynthetic process · negative regulation of fat cell differentiation · negative regulation of osteoblast differentiation · positive regulation of osteoclast differentiation · positive regulation of mitosis · negative regulation of transcription, DNA-dependent · positive regulation of transcription, DNA-dependent · positive regulation of transcription from RNA polymerase II promoter · positive regulation of transcription from RNA polymerase II promoter · positive regulation of translational initiation by iron · negative regulation of glucose import · positive regulation of JNK cascade · embryonic digestive tract development · positive regulation of smooth muscle cell proliferation · positive regulation of cytokine secretion · regulation of insulin secretion · positive regulation of synaptic transmission · defense response to Gram-positive bacterium · leukocyte tethering or rolling · negative regulation of lipid catabolic process · regulation of immunoglobulin secretion · positive regulation of membrane protein ectodomain proteolysis · positive regulation of sequence-specific DNA binding transcription factor activity · positive regulation of NF-kappaB transcription factor activity · positive regulation of protein transport · response to glucocorticoid stimulus · positive regulation of NFAT protein import into nucleus · positive regulation of hair follicle development · positive regulation of protein kinase B signaling cascade · induction of necroptosis by extracellular signals · positive regulation of vitamin D biosynthetic process · positive regulation of calcidiol 1-monooxygenase activity · epithelial cell proliferation involved in salivary gland morphogenesis · regulation of branching involved in salivary gland morphogenesis · negative regulation of branching involved in lung morphogenesis · necrotic cell death · positive regulation of ERK1 and ERK2 cascade · cellular response to amino acid stimulus · cellular response to nicotine · cellular response to organic cyclic compound · positive regulation of mononuclear cell migration · positive regulation of podosome assembly · extrinsic apoptotic signaling pathway · positive regulation of protein localization at cell surface · positive regulation of chemokine (C-X-C motif) ligand 2 production Sources: Amigo / QuickGO
RNA表达模式
更多表达数据
直系同源体
物种	人类	小鼠
Entrez	7124	21926
Ensembl	ENSG00000204490	ENSMUSG00000024401
UniProt	P01375	P06804
mRNA序列	NM_000594.3	NM_013693.2
蛋白序列	NP_000585.2	NP_038721.1
基因位置	Chr 6: 31.54 – 31.55 Mb	Chr 17: 35.2 – 35.2 Mb
PubMed查询	[1]	[2]
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功能

总括而言，肿瘤坏死因子能抑制不同种流感病毒的复制，拥有强大的抗病毒效果^[2]。肿瘤坏死因子的主要作用是调节免疫细胞的功能。作为一种内源性致热原，它能够促使发热，引起细胞凋亡，（通过诱使产生IL1和IL6（英语：Interleukin 6））引发败血症，引起恶病体质，引发炎症，阻止肿瘤发生和病毒复制（英语：Viral replication）。

肿瘤坏死因子生产的失调被认为与许多人类疾病有关，包括阿兹海默症^[3]、癌症^[4]、重性抑郁障碍^[5]和肠炎。^[6]虽然仍有争议，不过当前的研究认为肿瘤坏死因子α的水平与抑郁和肠炎有关。^[7]基因工程生产的肿瘤坏死因子被用作免疫兴奋剂（英语：Immunostimulant）（国际非专利药品名称为他索纳明）。肿瘤的恶变过程中，肿瘤坏死因子α常异位表达，而其过量表达同副甲状腺素一道与引发继发性高钙血症和癌症有关。

炎症过程中释放的TNF与H2O2诱导的BCa转化有关，伴血吸虫感染的BCa患者血清中TNF水平显著升高。另外，T3及T4期患者TNF水平高于T1及T2早期患者，提示TNF水平可能有助于BCa的进展^[8]。由于TNF有助于BCa的形成和发展，故而可以作为评估BCa侵袭性和恶性程度的指标^[9]。