RB1
小结
RB1是抑癌基因，也被称为Rb，编码蛋白参与细胞周期检查点，调节细胞周期进程。RB的以非磷酸化形式与E2F转录因子家族结合，其与E2F二聚化伴侣（E2F-DP）一起通过募集组蛋白脱乙酰酶（HDAC）抑制S期促进因子的转录并诱导异染色质形成。在G1结束时，细胞周期蛋白依赖性激酶（CDK）将RB磷酸化为pRB，这导致其与E2F-DP复合物解离，从而允许进入S期。RB保持磷酸化直至有丝分裂结束，此时它被蛋白磷酸酶1（PP1）去磷酸化以激活G1-S期检查点。除了其在G1细胞周期停滞中的作用外，RB1还在保护基因组稳定性和响应各种刺激时介导细胞凋亡，衰老和分化中起作用。RB1的功能丧失不仅导致细胞的不受调节分裂和生长，而且还导致废止了多种防止细胞转化和肿瘤发生的机制。RB1的功能丧失和缺失与许多人类癌症相关，包括肺癌，乳腺癌，前列腺癌和膀胱癌，并且RB1和p53的同时功能丧失被认为是构成肿瘤发生的起始事件。RB1基因的纯合性丢失或失活是视网膜母细胞瘤的标志，RB1的胚系突变和视网膜母细胞瘤以及其他癌症类型的风险增加相关。
RB1, also known as RB, is involved in the cell-cycle checkpoint and in its active form inhibits the transition from G1 to S phase of the cell cycle until the cell is ready to divide. RB is active in its unphosphorylated form where it binds to E2F family of transcription factors, which together with the E2F Dimerization Partner (E2F-DP), inhibits the transcription of S-phase promoting factors by recruiting histone deacetylases (HDACs) and induce heterochromatin formation. At the end of G1, cyclin-dependent kinases (CDKs) phosphorylate RB to pRB which leads to its dissociation from the E2F-DP complex, thereby allowing entry into S-phase. RB remains phosphorylated until the end of mitosis at which point it is dephosphorylated by protein phosphatase 1 (PP1) to activate the G1-S-phase checkpoint. In addition to its role in G1 cell cycle arrest, RB1 has also been shown to play a role in safeguarding genome stability and mediating apoptosis, senescence and differentiation in response to various stimuli. As a result of its role in these essential cellular functions, loss of function of RB1 not only leads to unregulated cell division and growth but also to the abrogation of multiple mechanisms that safeguard against cellular transformation and tumorigenesis. Loss-of-function and deletions of RB1 have been associated with many human cancers including lung, breast, prostate and bladder cancers, and concomitant loss of RB1 and p53 are thought to constitute a tumor-initiating event. Homozygous loss or inactivation of the RB1 gene is a hallmark of retinoblastoma, and germline mutations in RB1 and are at an increased risk of retinoblastoma as well as other cancer types.