Alternative titles; symbols
HGNC Approved Gene Symbol: CTDSPL2
Cytogenetic location: 15q15.3-q21.1 Genomic coordinates (GRCh38) : 15:44,427,629-44,529,038 (from NCBI)
Reversible phosphorylation of the C-terminal domain (CTD) of the RNA polymerase II large subunit (POLR2A; 180660) is crucial for coordinating transcription with RNA processing and histone modification. CTDSPL2 is a chromatin-associated CTD phosphatase that resides at transcriptionally silenced gene regions (Wani et al., 2016). CTDSPL2 also plays a critical role in epithelial-to-mesenchymal transition through dephosphorylation and stabilization of SNAIL (SNAI1; 604238) (Zhao et al., 2018).
Wani et al. (2016) stated that human CTDSPL2, which they called SCP4, contains 466 amino acids, including a C-terminal CTD phosphatase domain. Immunostaining and immunofluorescence analyses showed that SCP4 localized to nucleus, at the vicinity of the nuclear periphery, in HeLa cells. SCP4 preferentially associated with transcriptionally inactive chromosomal regions.
Gross (2020) mapped the CTDSPL2 gene to chromosome 15q15-q21.1 based on an alignment of the CTDSPL2 sequence (GenBank BC035744) with the genomic sequence (GRCh38).
Using RT-PCR analysis, Ma et al. (2010) found that CTDSPL2 expression was higher in human umbilical cord blood (UCB) than in adult bone marrow. CTDSPL2 expression increased during erythroid differentiation of K562 cells. Overexpression of CTDSPL2 in UCB-derived K562 cells increased hemoglobin-containing cells during erythroid differentiation and increased expression of epsilon-globin (HBE1; 142100) and gamma-globin (see HBG1, 142200) genes. Repression of CTDSPL2 in K562 cells decreased hemoglobin-containing cells and expression of epsilon- and gamma- globin, but it did not inhibit the increase of hemoglobin-containing cells during erythroid differentiation. Similarly, overexpression of CTDSPL2 in UCB-derived CD34 (142230)-positive hematopoietic progenitor cells (HPCs) increased transcription of all globin genes. Repression of CTDSPL2 decreased transcription of only the epsilon-globin gene, with little to no effect on other globin genes or on any globin genes after erythroid differentiation.
Using dephosphorylation assays, Wani et al. (2016) demonstrated that SCP4 functioned as a ser5-preferential CTD phosphatase. Fractionation analysis showed that chromatin-associated SCP4 underwent dynamic relocation from the nucleus to the cytoplasm during erythroid differentiation of K562 cells.
Zhao et al. (2018) found that ectopic expression of SCP4 in MCF10A human mammary epithelial cells enhanced TGFB (TGFB1; 190180)-induced epithelial-mesenchymal transition and promoted cell migration through regulation of SNAIL. In contrast, knockdown of SCP4 attenuated these parameters. SCP4 bound directly to the N-terminal region of SNAIL and promoted SNAIL stability by blocking its polyubiquitination through dephosphorylation of ser96 and ser100.
Gross, M. B. Personal Communication. Baltimore, Md. 1/14/2020.
Ma, Y.-N., Zhang, X., Yu, H.-C., Zhang, J.-W. CTD small phosphatase like 2 (CTDSPL2) can increase epsilon- and gamma-globin gene expression in K562 cells and CD34+ cells derived from umbilical cord blood. BMC Cell Biol. 11: 75, 2010. Note: Electronic Article. [PubMed: 20932329] [Full Text: https://doi.org/10.1186/1471-2121-11-75]
Wani, S., Sugita, A., Ohkuma, Y., Hirose, Y. Human SCP4 is a chromatin-associated CTD phosphatase and exhibits the dynamic translocation during erythroid differentiation. J. Biochem. 160: 111-120, 2016. [PubMed: 26920047] [Full Text: https://doi.org/10.1093/jb/mvw018]
Zhao, Y., Liu, J., Chen, F., Feng, X.-H. C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization. Open Biol. 8: 170274, 2018. Note: Electronic Article. [PubMed: 29618518] [Full Text: https://doi.org/10.1098/rsob.170274]