p53 Pathway
p53是最重要的肿瘤抑制基因之一,常被称为“基因组守护者”。 在几乎所有的癌症中,都存在 p53基因或其调控回路中的一部分发生基因突变,由此可见其重要性。它通过防止由细胞应激或DNA损伤导致突变来保护基因组的稳定性。 p53通过调节细胞凋亡、抑制细胞周期进程、细胞分化、细胞生长阻滞及加速DNA修复来维持基因组的稳定。
p53是在哺乳动物细胞中保持低水平的特异性DNA结合转录因子, p53具有非常短的半衰期,因而在非应激细胞内几乎检测不到。这主要是在 其抑制因子MDM2作用下,通过p53持续的泛素化和后期通过26S蛋白酶体降解实现。DNA损伤等细胞应激信号会抑制p53的泛素化,并导致其稳定和活化。一旦p53活化,将会与其下游目标的调控元件结合并调控其转录。从而可以启动基于p53的不同肿瘤抑制功能的多种细胞治疗方案。
血管生成
BAI1 (Brain-Specific Angiogenesis Inhibitor 1):
SERPINE1 (serpin Peptidase Inhibitor, Clade E (Nexin, Plasminogen Activator Inhibitor Type 1), Member 1):
PRSS55 (Protease, Serine, 55):
SERPINB5 (serpin Peptidase Inhibitor, Clade B (Ovalbumin), Member 5):
细胞凋亡
APAF1 (Apoptotic Peptidase Activating Factor 1):
PIDD (P53-Induced Death Domain Protein):
BBC3 (BCL2 Binding Component 3):
BAX (BCL2-Associated X Protein):
FAS (Fas (TNF Receptor Superfamily, Member 6)):
MRPL41 (Mitochondrial Ribosomal Protein L41):
TNFRSF10B (Tumor Necrosis Factor Receptor Superfamily, Member 10b):
TP53I3 (Tumor Protein P53 Inducible Protein 3):
核心调整
NRAS - GTPase NRas:
MDM2 (Mdm2, p53 E3 Ubiquitin Protein Ligase Homolog (Mouse)):
DNA修复
RRM2B (Ribonucleotide Reductase M2 B (TP53 Inducible)):
XPC (Xeroderma Pigmentosum, Complementation Group C):
CRLF3 (Cytokine Receptor-Like Factor 3):
反应器
PRDX1 - Peroxiredoxin 1:
PPP1R13B (Protein Phosphatase 1, Regulatory Subunit 13B):
KAT2B (K(lysine) Acetyltransferase 2B):
PAG1 (phosphoprotein Associated with Glycosphingolipid Microdomains 1):
TANK (TRAF Family Member-Associated NFKB Activator):
生长抑制
CDKN1A (Cyclin-Dependent Kinase Inhibitor 1A (p21, Cip1)):
GADD45A (Growth Arrest and DNA-Damage-Inducible, alpha):
SFN - Stratifin:
间介器
ATM (Ataxia Telangiectasia Mutated):
HMGB1 (High Mobility Group Box 1):
ARFGAP1 (ADP-Ribosylation Factor GTPase Activating Protein 1):
ATR (Ataxia Telangiectasia and Rad3 Related):
CHEK1 (Checkpoint Kinase 1):
CHEK2 (Checkpoint Kinase 2):
NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1):
PML (Promyelocytic Leukemia):
SCYL1 (SCY1-Like 1 (S. Cerevisiae)):
TRIM29 (Tripartite Motif Containing 29):
致癌基因激活
HRAS (HRas proto-oncogene, GTPase):
DMP1 (Dentin Matrix Acidic phosphoprotein 1):
E2F1 (E2F Transcription Factor 1):
NRAS - GTPase NRas:
TBX2 (T-Box 2):
TWIST1 (Twist Homolog 1 (Drosophila)):
其他
CCNG1 - Cyclin G1:
MAP4 (Microtubule-Associated Protein 4):
PPM1D (Protein Phosphatase, Mg2+/Mn2+ Dependent, 1D):
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