PIDD1 (p53-induced death domain protein 1)
- symbol:
- PIDD1
- locus group:
- protein-coding gene
- location:
- 11p15.5
- gene_family:
- alias symbol:
- MGC16925|DKFZp434D229
- alias name:
- None
- entrez id:
- 55367
- ensembl gene id:
- ENSG00000177595
- ucsc gene id:
- None
- refseq accession:
- NM_145886
- hgnc_id:
- HGNC:16491
- approved reserved:
- 2001-09-04
PIDD1（也称为LRDD或p53-induced protein with a death domain 1）是一个由TP53基因（即著名的抑癌基因p53）调控的基因，编码一种含有死亡结构域（death domain，一种介导蛋白质相互作用和细胞凋亡信号传递的结构）的蛋白质。PIDD1的主要功能与细胞应激反应相关，特别是在DNA损伤或细胞压力条件下被激活，参与调控细胞凋亡（程序性细胞死亡）或细胞存活。它通过形成多蛋白复合物发挥作用，例如与RIPK1和Caspase-2结合形成PIDDosome复合物，从而激活Caspase-2并触发凋亡。PIDD1的表达水平受p53直接调控，是p53下游靶基因之一。突变或异常表达可能影响其功能，例如某些突变可能导致PIDD1无法正常形成复合物，从而削弱细胞凋亡能力，与肿瘤发生或化疗耐药性相关。研究发现PIDD1在多种癌症中表达异常，如神经母细胞瘤和结直肠癌，可能作为促癌或抑癌因子取决于上下文环境。过表达PIDD1可能增强细胞凋亡，但长期激活也可能导致组织损伤；而低表达可能减少凋亡，促进细胞异常增殖。PIDD1属于含有死亡结构域的蛋白质家族（death domain-containing protein family），该家族成员通常参与凋亡、炎症和免疫反应的信号传导。这类蛋白质通过死亡结构域与其他分子相互作用，形成信号复合物。目前PIDD1的中文译名较统一，但需注意其别名如“LRDD”或“死亡结构域p53诱导蛋白1”可能在不同文献中出现。其功能复杂性体现在既可促凋亡，又在某些情况下通过NF-κB通路促进存活，这种双重角色使其在癌症和神经退行性疾病研究中备受关注。
The protein encoded by this gene contains a leucine-rich repeat and a death domain. This protein has been shown to interact with other death domain proteins, such as Fas (TNFRSF6)-associated via death domain (FADD) and MAP-kinase activating death domain-containing protein (MADD), and thus may function as an adaptor protein in cell death-related signaling processes. The expression of the mouse counterpart of this gene has been found to be positively regulated by the tumor suppressor p53 and to induce cell apoptosis in response to DNA damage, which suggests a role for this gene as an effector of p53-dependent apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]
Gene Ontology
Subcellular localization of PIDD1 (and its protein):
- plasma membrane
- cytoplasm
- extracellular
- golgi
- vesicle
- cytoskeleton
- endoplasmic reticulum
- nucleus
- endosome
- lysosome
- mitochondrion
Gene Ontology (GO) terms for PIDD1:
| Interacting Gene | Interaction | Source/Score |
| Name |
|---|
| 4064 NF-kappa B signaling pathway [PATH:hsa04064] |
| 4115 p53 signaling pathway [PATH:hsa04115] |
| Disease | Score | NofPmids | NofSnps | Source |
| Renal Cell Carcinoma | 0.12 | 1 | 0 | CTD_human |
| Squamous cell carcinoma | 0.00272435 | 1 | 0 | LHGDN |
| Cessation of life | 0.00272435 | 1 | 0 | LHGDN |
| melanoma | 0.000271442 | 1 | 0 | BeFree |
| Neutropenia | 0.000271442 | 1 | 0 | BeFree |
| Leukopenia | 0.000271442 | 1 | 0 | BeFree |
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