通过甲基化调节TP53活性

中文名称

通过甲基化调节TP53活性

通路描述

TP53（p53）在多个赖氨酸和精氨酸残基上发生甲基化，从而调节其转录活性。PRMT5作为ATM激活复合物的一部分（包括TTC5、JMY和EP300/p300）招募到TP53上，对TP53的赖氨酸残基R333、R335和R337进行甲基化。PRMT5介导的甲基化促进TP53刺激细胞周期停滞基因的表达（Shikama et al. 1999, Demonacos et al. 2001, Demonacos et al. 2004, Adams et al. 2008, Adams et al. 2012）。SETD9（SET9）在TP53赖氨酸残基K372上甲基化，导致TP53稳定性和活性的增加（Chuikov et al. 2004, Couture et al. 2006, Bai et al. 2011）。SMYD2介导的TP53赖氨酸残基K370甲基化抑制TP53转录活性（Huang et al. 2006）。甲基转移酶复合物EHMT1和EHMT2对TP53赖氨酸残基K373的二甲基化也抑制TP53介导的转录（Huang et al. 2010）。染色质紧缩因子L3MBTL1结合SETD8（SET8）甲基化TP53赖氨酸K382的TP53单体，并通过改变局部染色质架构抑制TP53靶基因的转录（West et al. 2010）。组蛋白赖氨酸特异性去甲基化酶LSD1与TP53相互作用并抑制p53介导的转录激活（Huang et al. 2007）。PRMT1和CARM1也可以协同方式调节p53功能（An et al. 2004）。

英文描述

Cancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare familial syndrome basal cell nevus syndrome (BCNS, or Gorlin syndrome) that predisposes to development of BCC. In addition, there is strong epidemiological and genetic evidence that demonstrates UV exposure as a risk factor of prime importance. The development of basal cell carcinoma is associated with constitutive activation of sonic hedgehog signaling. The mutations in SMOH, PTCH1, and SHH in BCCs result in continuous activation of target genes. At a cellular level, sonic hedgehog signaling promotes cell proliferation. Mutations in TP53 are also found with high frequency (>50%) in sporadic BCC.

所含基因

63 个基因

APC APC2 AXIN1 AXIN2 BAK1 BAX BMP2 BMP4 CDKN1A CTNNB1 DDB2 DVL1 DVL2 DVL3 FZD1 FZD10 FZD2 FZD3 FZD4 FZD5 FZD6 FZD7 FZD8 FZD9 GADD45A GADD45B GADD45G GLI1 GLI2 GLI3 GSK3B HHIP KIF7 LEF1 POLK PTCH1 PTCH2 SHH SMO SUFU TCF7 TCF7L1 TCF7L2 TP53 WNT1 WNT10A WNT10B WNT11 WNT16 WNT2 WNT2B WNT3 WNT3A WNT4 WNT5A WNT5B WNT6 WNT7A WNT7B WNT8A WNT8B WNT9A WNT9B