RUNX2 调控与细胞迁移相关的基因
中文名称
通路描述
RUNX2 调控在正常发育及乳腺癌细胞骨转移过程中涉及细胞迁移的多个基因的表达。RUNX2 刺激 ITGA5 基因转录，编码整合素 alpha-5，促进乳腺癌细胞与骨的粘附，从而促进骨转移的形成。ITGA5 也涉及人类牙髓干细胞迁移。在斑马鱼中，整合素 alpha-5 协调发育中感觉器官的细胞迁移。在鼠视网膜血管生成中，整合素 alpha-5 调节内皮细胞迁移。ITGBL1 基因编码整合素 beta 样蛋白 1，涉及 TGF-beta 信号通路调节及 RUNX2 诱导的乳腺癌骨转移。RUNX2 介导的 MMP13 基因转录（编码基质金属蛋白酶 13）由 AKT 介导的 RUNX2 磷酸化刺激，与乳腺癌细胞侵袭性相关。MMP13 参与免疫细胞在损伤后的迁移以及骨骼组织的重塑。
英文描述
Phosphorylation and nuclear translocation of the CRY:PER:kinase complex Cryptochrome proteins (CRY1, CRY2) and Period proteins (PER1, PER2, PER3) are translated in the cytosol. CDK5 phosphoryates PER2 in the cytosol and phosphorylated PER2 interacts with CRY1 (inferred from mouse homologs in Brenna et al. 2019). The heterodimer associates with kinases Casein kinase I delta (CSNK1D) and Casein kinase I epsilon (CSNK1E) and other CRY and PER proteins in a large complex in the cytosol (inferred from mouse homologs in Nangle et al. 2014, Aryal et al. 2017) and the CRY and PER proteins are phosphorylated by CSNK1D and CSNK1E (Toh et al. 2001, Camacho et al. 2001, inferred from mouse homologs in Akashi et al. 2002, Eide et al. 2002, reviewed in Hirano et al. 2016, Yang et al. 2017, Ode et al. 2018, Narasimamurthy and Virshup 2021). The large complex containing the phosphorylated CRY and PER proteins is then translocated into the nucleus (inferred from mouse homologs in Kume et al. 1999, Vielhaber et al. 2000, Aryal et al. 2017, Cao et al. 2023), though there is a discrepancy in the measured sizes of the nuclear complex. Cao et al. (2023) used gel exclusion chromatography and glycerol gradient centrifugation and found a mass of 707 kDa: Aryal et al. (2017) used a novel electrophoretic method and found a mass of 1.9 MDa. The large CRY:PER:kinase complex then associates with phosphorylated BMAL1:CLOCK heterodimers (and likely with BMAL1:NPAS2 heterodimers) and represses the transactivation activity of BMAL1:CLOCK (inferred from mouse homologs in Griffin et al. 1999, Ye et al. 2014, Chiou et al. 2016, Cao et al. 2021).
所含基因
14 个基因