Rallabandi Harikrishna Reddy, Ganesan Palanivel, Kim Young Jun
Department of Medicinal Biosciences and Nanotechnology Research Center, Konkuk University, Chungju 27478, Korea.
Life (Basel). 2020 May 8;10(5):57. doi: 10.3390/life10050057.
The human C-terminal domain small phosphatase 1 (CTDSP1/SCP1) is a protein phosphatase with a conserved catalytic site of DXDXT/V. CTDSP1's major activity has been identified as dephosphorylation of the 5th Ser residue of the tandem heptad repeat of the RNA polymerase II C-terminal domain (RNAP II CTD). It is also implicated in various pivotal biological activities, such as acting as a driving factor in repressor element 1 (RE-1)-silencing transcription factor (REST) complex, which silences the neuronal genes in non-neuronal cells, G1/S phase transition, and osteoblast differentiation. Recent findings have denoted that negative regulation of CTDSP1 results in suppression of cancer invasion in neuroglioma cells. Several researchers have focused on the development of regulating materials of CTDSP1, due to the significant roles it has in various biological activities. In this review, we focused on this emerging target and explored the biological significance, challenges, and opportunities in targeting CTDSP1 from a drug designing perspective.
人C末端结构域小磷酸酶1（CTDSP1/SCP1）是一种蛋白磷酸酶，具有保守的DXDXT/V催化位点。CTDSP1的主要活性已被确定为RNA聚合酶II C末端结构域（RNAP II CTD）串联七肽重复序列第5个丝氨酸残基的去磷酸化。它还参与各种关键的生物学活动，例如作为阻遏元件1（RE-1）-沉默转录因子（REST）复合物中的驱动因子，该复合物使非神经元细胞中的神经元基因沉默、G1/S期转换和成骨细胞分化。最近的研究结果表明，CTDSP1的负调控导致神经胶质瘤细胞中癌症侵袭的抑制。由于CTDSP1在各种生物学活动中具有重要作用，一些研究人员专注于CTDSP1调节材料的开发。在本综述中，我们聚焦于这个新兴靶点，从药物设计的角度探讨了靶向CTDSP1的生物学意义、挑战和机遇。
