成骨细胞分化
中文名称
通路描述
RUNX2 与 CBFB 复合物调节成骨细胞分化相关基因的转录。RUNX2 刺激 BGLAP 基因的转录，编码骨钙素（Ducy and Karsenty 1995, Ducy et al. 1997）。当 RUNX2 在 serine 残基 S451 上磷酸化时，RUNX2:CBFB 复合物与 BGLAP 基因启动子的结合增加（Wee et al. 2002）。骨钙素是一种从骨中产生的激素，是骨细胞外基质中最丰富的非胶原蛋白之一（综述 Karsenty 和 Olson 2016）。激活的雄激素受体（AR）与 RUNX2 结合可防止 RUNX2 与 BGLAP 启动子结合（Baniwal et al. 2009）。当 YAP1 与 SRC 和/或 YES1 磷酸化后与 RUNX2 结合 BGLAP 基因启动子时，BGLAP 基因的转录被抑制（Zaidi et al. 2004）。SRC 的信号已知抑制成骨细胞分化（Marzia et al. 2000）。RUNX2 和 SP7（Osterix，也称为 OSX）同时结合 UCMA 启动子中相邻的 RUNX2 和 SP7 结合位点，协同激活 UCMA 转录。UCMA 刺激成骨细胞分化和矿化结节形成（Lee et al. 2015）。SCF（SKP2）E3 泛素连接酶复合物通过多泛素化 RUNX2 并将其靶向蛋白酶体介导的降解抑制成骨细胞分化（Thacker et al. 2016）。该过程在成骨细胞中通过葡萄糖摄取被抑制（Wei et al. 2015）。
英文描述
RUNX2 regulates osteoblast differentiation The complex of RUNX2 and CBFB regulates transcription of genes involved in differentiation of osteoblasts.
RUNX2 stimulates transcription of the BGLAP gene, encoding osteocalcin (Ducy and Karsenty 1995, Ducy et al. 1997). Binding of the RUNX2:CBFB complex to the BGLAP gene promoter is increased when RUNX2 is phosphorylated on serine residue S451 (Wee et al. 2002). Osteocalcin, a bone-derived hormone, is one of the most abundant non-collagenous proteins of the bone extracellular matrix (reviewed in Karsenty and Olson 2016). Association of the activated androgen receptor (AR) with RUNX2 prevents binding of RUNX2 to the BGLAP promoter (Baniwal et al. 2009). When YAP1, tyrosine phosphorylated by SRC and/or YES1, binds to RUNX2 at the BGLAP gene promoter, transcription of the BGLAP gene is inhibited (Zaidi et al. 2004). Signaling by SRC is known to inhibit osteoblast differentiation (Marzia et al. 2000).
Simultaneous binding of RUNX2 and SP7 (Osterix, also known as OSX) to adjacent RUNX2 and SP7 binding sites, respectively, in the UCMA promoter, synergistically activates UCMA transcription. UCMA stimulates osteoblast differentiation and formation of mineralized nodules (Lee et al. 2015).
The SCF(SKP2) E3 ubiquitin ligase complex inhibits differentiation of osteoblasts by polyubiquitinating RUNX2 and targeting it for proteasome-mediated degradation (Thacker et al. 2016). This process is inhibited by glucose uptake in osteoblasts (Wei et al. 2015).
RUNX2 stimulates transcription of the BGLAP gene, encoding osteocalcin (Ducy and Karsenty 1995, Ducy et al. 1997). Binding of the RUNX2:CBFB complex to the BGLAP gene promoter is increased when RUNX2 is phosphorylated on serine residue S451 (Wee et al. 2002). Osteocalcin, a bone-derived hormone, is one of the most abundant non-collagenous proteins of the bone extracellular matrix (reviewed in Karsenty and Olson 2016). Association of the activated androgen receptor (AR) with RUNX2 prevents binding of RUNX2 to the BGLAP promoter (Baniwal et al. 2009). When YAP1, tyrosine phosphorylated by SRC and/or YES1, binds to RUNX2 at the BGLAP gene promoter, transcription of the BGLAP gene is inhibited (Zaidi et al. 2004). Signaling by SRC is known to inhibit osteoblast differentiation (Marzia et al. 2000).
Simultaneous binding of RUNX2 and SP7 (Osterix, also known as OSX) to adjacent RUNX2 and SP7 binding sites, respectively, in the UCMA promoter, synergistically activates UCMA transcription. UCMA stimulates osteoblast differentiation and formation of mineralized nodules (Lee et al. 2015).
The SCF(SKP2) E3 ubiquitin ligase complex inhibits differentiation of osteoblasts by polyubiquitinating RUNX2 and targeting it for proteasome-mediated degradation (Thacker et al. 2016). This process is inhibited by glucose uptake in osteoblasts (Wei et al. 2015).
所含基因
26 个基因