TP53 调控参与 G1 细胞周期停滞的基因转录
中文名称
通路描述
TP53 是 G1 细胞周期停滞中最主要的靶基因之一，其作用是通过抑制 CDKN1A（p21）的表达来阻止 G1/S 转换。CDKN1A 与 CDK2 或 CDK2 与 CCNA/CCNE 复合物结合并使其失活，从而防止细胞进入 S 期。此外，TP53 还能诱导 E2F7 表达，该蛋白通过抑制 E2F1 来促进 G1 停滞。在应激条件下，TP53 可能通过诱导 PCBP4 来稳定 CDKN1A mRNA，从而维持 G1 停滞。同时，TP53 通过 ARID3A 等共调节因子进一步调控 CDKN1A 的表达，以决定细胞是走向 G2 停滞还是凋亡。
英文描述
Regulation of CDH19 Expression and Function Cadherin-19 (CDH19, also known as CDH7L2) is a classical type II cadherin. The human CDH19 gene is a part of the cadherin gene cluster at the chromosomal bands 18q22-q23, together with CDH7 and CDH20 (Kools et al. 2000). At the plasma membrane, CDH19 associates with alpha-catenin (CTNNA1), beta-catenin (CTNNB1), gamma-catenin (JUP) and delta catenin (CTNND1) (Huang et al. 2022), like other classical type I and type II cadherins. CDH19 possesses five extracellular cadherin domains and, like other classical cadherins, is thought to play a role in the establishment of homotypic cell-cell adhesions during formation of adherens junctions.
In rat, the expression of Cdh19 overlaps with the expression of the neural crest cell marker Sox10 (Takahashi and Osumi 2005). In mouse, it was shown that Sox10 transcription factor, essential for migration of neural crest cells during formation of the enteric nervous system, binds to the Cdh19 gene promoter and stimulates Cdh19 transcription. Cdh19 knockdown results in retarded sacral migration of neural crest cells, while re-expression of Cdh19 partially rescues retarded migration of Sox10-null neural crest cells (Huang et al. 2022). CDH19 is a specific marker of Schwann cell precursors (Takahashi and Osumi 2005, Iribar et al. 2016, Stratton et al. 2017, George et al. 2018, Woods et al. 2021).
During angiogenesis, in response to monocyte chemotactic protein 1 (MCP-1, also known as CCL2 or C-C motif chemokine 2), CDH19 transcription is directly stimulated by ZC3H12A (MCPIP, for MCP-1 induced protein) (Niu et al. 2008, Niu et al. 2013). CDH19 was found to be a target of microRNA miR-197-5p. The circular RNA hsa_circ_006220 was shown to sponge miR-197-5p and lead to upregulation of CDH19 mRNA and protein levels (Shi et al. 2021). Circular RNAs that possess multiple microRNA binding sites act as sponges that, by binding to microRNAs, prevent these microRNAs from associating with their target mRNAs.
Both upregulation and downregulation of CDH19 have been reported in cancer and it has been proposed to play both oncogenic and tumor-suppressive roles, depending on the cancer type. CDH19 mRNA is upregulated in clear-cell sarcoma and correlates with a hypomethylated profile (Dermawan et al. 2022). In glioblastoma, CDH19 is upregulated in cancer stem-like cells (Zorniak et al. 2015). In colorectal tumors, CDH19 is upregulated compared to normal tissue (Bujko et al. 2015). In triple negative breast cancer, CDH19 was proposed to play a tumor suppressor role (Shi et al. 2021). A homozygous deletion of the CDH19 gene was reported in a portion of chondrosarcoma tumor samples (Niini et al. 2012).
In rat, the expression of Cdh19 overlaps with the expression of the neural crest cell marker Sox10 (Takahashi and Osumi 2005). In mouse, it was shown that Sox10 transcription factor, essential for migration of neural crest cells during formation of the enteric nervous system, binds to the Cdh19 gene promoter and stimulates Cdh19 transcription. Cdh19 knockdown results in retarded sacral migration of neural crest cells, while re-expression of Cdh19 partially rescues retarded migration of Sox10-null neural crest cells (Huang et al. 2022). CDH19 is a specific marker of Schwann cell precursors (Takahashi and Osumi 2005, Iribar et al. 2016, Stratton et al. 2017, George et al. 2018, Woods et al. 2021).
During angiogenesis, in response to monocyte chemotactic protein 1 (MCP-1, also known as CCL2 or C-C motif chemokine 2), CDH19 transcription is directly stimulated by ZC3H12A (MCPIP, for MCP-1 induced protein) (Niu et al. 2008, Niu et al. 2013). CDH19 was found to be a target of microRNA miR-197-5p. The circular RNA hsa_circ_006220 was shown to sponge miR-197-5p and lead to upregulation of CDH19 mRNA and protein levels (Shi et al. 2021). Circular RNAs that possess multiple microRNA binding sites act as sponges that, by binding to microRNAs, prevent these microRNAs from associating with their target mRNAs.
Both upregulation and downregulation of CDH19 have been reported in cancer and it has been proposed to play both oncogenic and tumor-suppressive roles, depending on the cancer type. CDH19 mRNA is upregulated in clear-cell sarcoma and correlates with a hypomethylated profile (Dermawan et al. 2022). In glioblastoma, CDH19 is upregulated in cancer stem-like cells (Zorniak et al. 2015). In colorectal tumors, CDH19 is upregulated compared to normal tissue (Bujko et al. 2015). In triple negative breast cancer, CDH19 was proposed to play a tumor suppressor role (Shi et al. 2021). A homozygous deletion of the CDH19 gene was reported in a portion of chondrosarcoma tumor samples (Niini et al. 2012).
所含基因
7 个基因