생명과학회지 (Journal of Life Science)

  • 제27권3호
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  • Pages.370-381
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  • 2017
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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CTD 탈 인산화 효소의 기능과 역할

Emerging Roles of CTD Phosphatases

  • 김영준 (건국대학교 의생명화학과)
  • Kim, Youngjun (Department of Biomedical Chemistry and Nanotechnology Research Center, Konkuk University)
  • 투고 : 2017.03.14
  • 심사 : 2017.03.27
  • 발행 : 2017.03.30
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초록

단백질 탈 인산화는 단백질 탈 인산화 효소에 의해 매개되는 과정으로 세포 생존에 매우 중요하다. 단백질 탈 인산화 효소 중에서 최근 CTD (carboxy-terminal domain) 탈 인산화 효소들이 등장하고 있으며 이들에 대한 새로운 생물학적 역할이 밝혀지고 있다. 이 효소의 그룹에는CTD 탈 인산화 효소 1(CTDP1), CTD 소형 탈 인산화 효소 1(CTDSP1), CTD 소형 탈 인산화 효소 2(CTDSP2), CTD 소형 탈 인산화 효소 유사(CTDSPL), CTD 소형 탈 인산화 효소 유사 2(CTDSPL2), CTD 핵 탈 인산화 효소(CTDNEP1) 및 유비퀴틴 유사 도메인 함유CTD 탈 인산화 효소 1(UBLCP1)들이 존재한다. CTDP1은 RNA 중합 효소 II (RNAPII)의 CTD의 두 번째 인산화 된 세린을 탈 인산화 시키고, CTDSP1, STDSP2 및 CTDSPL은 RNAPII의 CTD의 다섯 번째 인산화 된 세린을 탈 인산화 시킨다. 그리고 CTDSP1은 SMAD들, CDCA3, Twist1, 종양억제 단백질인 PML, c-Myc과 같은 새로운 기질을 탈 인산화 시키는 것으로 밝혀지고 있다. CTDP1은 유사 분열 조절 및 암세포 성장과 관련이 있다. CTDSP1, CTDSP2 및 CTDSPL은 종양 억제 기능 및 줄기 세포 분화와 관련이 있다. CTDNEP1은 LIPIN1을 탈 인산화 시키고 핵막 형성과 관련이 있다. CTDSPL2는 조혈 줄기 세포 분화와 관련이 있다. UBLCP1은 26S 프로테아좀을 탈 인산화 시키고 핵 프로테아좀 활성 조절과 관련이 있다. 결론적으로, CTD 탈 인산화 효소의 새로운 기능과 역할은 최근의 연구에서 밝혀지고 있으며, 이 리뷰는 CTD 탈 인산화 효소의 새롭게 밝혀진 역할들을 요약하고자 정리한 것이다.

Protein dephosphorylation is important for cellular regulation, which is catalyzed by protein phosphatases. Among protein phosphatases, carboxy-terminal domain (CTD) phosphatases are recently emerging and new functional roles of them have been revealed. There are 7 CTD phosphatases in human genome, which are composed of CTD phosphatase 1 (CTDP1), CTD small phosphatase 1 (CTDSP1), CTD small phosphatase 2 (CTDSP2), CTD small phosphatase-like (CTDSPL), CTD small phosphatase-like 2 (CTDSPL2), CTD nuclear envelope phosphatase (CTDNEP1), and ubiquitin-like domain containing CTD phosphatase 1 (UBLCP1). CTDP1 dephosphorylates the second phosphor-serine of CTD of RNA polymerase II (RNAPII), while CTDSP1, STDSP2, and CTDSPL dephosphorylate the fifth phosphor-serine of CTD of RNAPII. In addition, CTDSP1 dephosphorylates new substrates such as mothers against decapentaplegic homologs (SMADs), cell division cycle-associated protein 3 (CDCA3), Twist1, tumor-suppressor protein promyelocytic leukemia (PML), and c-Myc. CTDP1 is related to RNA polymerase II complex recycling, mitosis regulation and cancer cell growth. CTDSP1, CTDSP2 and CTDSPL are related to transcription factor recruitment, tumor suppressor function and stem cell differentiation. CTDNEP1 dephosphorylates LIPIN1 and is related to neural tube formation and nuclear envelope formation. CTDSPL2 is related to hematopoietic stem cell differentiation. UBLCP1 dephosphorylates 26S proteasome and is related to nuclear proteasome regulation. In conclusion, noble roles of CTD phosphatases are emerging through recent researches and this review is intended to summarize emerging roles of CTD phosphatases.

키워드

참고문헌

  1. Anedchenko, E. A., Dmitriev, A. A., Krasnov, G. S., Kondrat'eva, T. T., Kopantsev, E. P. and Vinogradova, T. V., et al. 2008. Down-regulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 genes in non-small cell lung cancer. Mol. Biol. (Mosk.) 42, 965-976.
  2. Anedchenko, E. A., Kiseleva, N. P., Dmitriev, A. A., Kiselev, F. L., Zabarovskii, E. R. and Senchenko, V. N. 2007. Tumor suppressor gene RBSP3 in cervical carcinoma: copy number and transcriptional level. Mol. Biol. (Mosk.) 41, 86-95. https://doi.org/10.1134/S0026893307010128
  3. Bahmanyar, S. 2015. Spatial regulation of phospholipid synthesis within the nuclear envelope domain of the endoplasmic reticulum. Nucleus 6, 102-106. https://doi.org/10.1080/19491034.2015.1010942
  4. Bahmanyar, S., Biggs, R., Schuh, A. L., Desai, A., Muller-Reichert, T. and Audhya, A., et al. 2014. Spatial control of phospholipid flux restricts endoplasmic reticulum sheet formation to allow nuclear envelope breakdown. Genes Dev. 28, 121-126. https://doi.org/10.1101/gad.230599.113
  5. Barbosa, A. D., Sembongi, H., Su, W. M., Abreu, S., Reggiori, F., Carman, G. M. and Siniossoglou, S. 2015. Lipid partitioning at the nuclear envelope controls membrane biogenesis. Mol. Biol. Cell 26, 3641-3657. https://doi.org/10.1091/mbc.E15-03-0173
  6. Buratowski, S. 2009. Progression through the RNA polymerase II CTD cycle. Mol. Cell 36, 541-546. https://doi.org/10.1016/j.molcel.2009.10.019
  7. Campbell, J. L., Lorenz, A., Witkin, K. L., Hays, T., Loidl, J. and Cohen-Fix, O. 2006. Yeast nuclear envelope subdomains with distinct abilities to resist membrane expansion. Mol. Biol. Cell 17, 1768-1778. https://doi.org/10.1091/mbc.E05-09-0839
  8. Dai, M., Al-Odaini, A. A., Arakelian, A., Rabbani, S. A., Ali, S. and Lebrun, J. J. 2012. A novel function for p21Cip1 and acetyltransferase p/CAF as critical transcriptional regulators of TGFbeta-mediated breast cancer cell migration and invasion. Breast Cancer Res. 14, R127.
  9. Denu, J. M., Stuckey, J. A., Saper, M. A. and Dixon, J. E. 1996. Form and function in protein dephosphorylation. Cell 87, 361-364. https://doi.org/10.1016/S0092-8674(00)81356-2
  10. Dixon, D. P., Fordham-Skelton, A. P. and Edwards, R. 2005. Redox regulation of a soybean tyrosine-specific protein phosphatase. Biochemistry 44, 7696-7703. https://doi.org/10.1021/bi047324a
  11. Egloff, S. and Murphy, S. 2008. Cracking the RNA polymerase II CTD code. Trends Genet. 24, 280-288. https://doi.org/10.1016/j.tig.2008.03.008
  12. Fawcett, K. A., Grimsey, N., Loos, R. J., Wheeler, E., Daly, A. and Soos, M., et al. 2008. Evaluating the role of LPIN1 variation in insulin resistance, body weight, and human lipodystrophy in U.K. Populations. Diabetes 57, 2527-2533. https://doi.org/10.2337/db08-0422
  13. Fu, H., Yang, D., Wang, C., Xu, J., Wang, W., Yan, R. and Cai, Q. 2015. Carboxy-terminal domain phosphatase 1 silencing results in the inhibition of tumor formation ability in gastric cancer cells. Oncol. Lett. 10, 2947-2952. https://doi.org/10.3892/ol.2015.3693
  14. Guo, X., Engel, J. L., Xiao, J., Tagliabracci, V. S., Wang, X., Huang, L. and Dixon, J. E. 2011. UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity. Proc. Natl. Acad. Sci. USA 108, 18649-18654. https://doi.org/10.1073/pnas.1113170108
  15. Han, S., Bahmanyar, S., Zhang, P., Grishin, N., Oegema, K. and Crooke, R., et al. 2011. Nuclear envelope phosphatase 1-regulatory subunit 1 (formerly TMEM188) is the metazoan Spo7p ortholog and functions in the lipin activation pathway. J. Biol. Chem. 287, 3123-3137.
  16. Han, S., Binns, D. D., Chang, Y. F. and Goodman, J. M. 2015. Dissecting seipin function: the localized accumulation of phosphatidic acid at ER/LD junctions in the absence of seipin is suppressed by Sei1p(DeltaNterm) only in combination with Ldb16p. BMC Cell Biol. 16, 29. https://doi.org/10.1186/s12860-015-0075-3
  17. Hausmann, S. and Shuman, S. 2002. Characterization of the CTD phosphatase Fcp1 from fission yeast. Preferential dephosphorylation of serine 2 versus serine 5. J. Biol. Chem. 277, 21213-21220. https://doi.org/10.1074/jbc.M202056200
  18. Hayata, T., Ezura, Y., Asashima, M., Nishinakamura, R. and Noda, M. 2015. Dullard/Ctdnep1 regulates endochondral ossification via suppression of TGF-beta signaling. J. Bone Miner. Res. 30, 947. https://doi.org/10.1002/jbmr.2479
  19. Irie, K., Takase, M., Araki, H. and Oshima, Y. 1993. A gene, SMP2, involved in plasmid maintenance and respiration in Saccharomyces cerevisiae encodes a highly charged protein. Mol. Gen. Genet. 236, 283-288.
  20. Kashuba, V. I., Li, J., Wang, F., Senchenko, V. N., Protopopov, A. and Malyukova, A., et al. 2004. RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignancies. Proc. Natl. Acad. Sci. USA 101, 4906-4911. https://doi.org/10.1073/pnas.0401238101
  21. Kashuba, V. I., Pavlova, T. V., Grigorieva, E. V., Kutsenko, A., Yenamandra, S. P. and Li, J., et al. 2009. High mutability of the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) in cancer. PLoS One 4, e5231. https://doi.org/10.1371/journal.pone.0005231
  22. Khan, M. A., Tania, M., Wei, C., Mei, Z., Fu, S. and Cheng, J., et al. 2015. Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition. Oncotarget 6, 19580-19591.
  23. Kim, H., Erickson, B., Luo, W., Seward, D., Graber, J. H. and Pollock, D. D., et al. 2010. Gene-specific RNA polymerase II phosphorylation and the CTD code. Nat. Struct. Mol. Biol. 17, 1279-1286. https://doi.org/10.1038/nsmb.1913
  24. Kim, Y., Gentry, M. S., Harris, T. E., Wiley, S. E., Lawrence, J. C. Jr. and Dixon, J. E. 2007. A conserved phosphatase cascade that regulates nuclear membrane biogenesis. Proc. Natl. Acad. Sci. USA 104, 6596-6601. https://doi.org/10.1073/pnas.0702099104
  25. Kim, Y. J. and Bahk, Y. Y. 2014. A study of substrate specificity for a CTD phosphatase, SCP1, by proteomic screening of binding partners. Biochem. Biophys. Res. Commun. 448, 189-194. https://doi.org/10.1016/j.bbrc.2014.04.089
  26. Kloet, D. E., Polderman, P. E., Eijkelenboom, A., Smits, L. M., van Triest, M. H. and van den Berg, M. C., et al. 2015. FOXO target gene CTDSP2 regulates cell cycle progression through Ras and p21(Cip1/Waf1). Biochem. J. 469, 289-298. https://doi.org/10.1042/BJ20140831
  27. Lin, Y. C., Lu, L. T., Chen, H. Y., Duan, X., Lin, X. and Feng, X. H., et al. 2014. SCP phosphatases suppress renal cell carcinoma by stabilizing PML and inhibiting mTOR/HIF signaling. Cancer Res. 74, 6935-6946. https://doi.org/10.1158/0008-5472.CAN-14-1330
  28. Lindegaard, B., Larsen, L. F., Hansen, A. B., Gerstoft, J., Pedersen, B. K. and Reue, K. 2007. Adipose tissue lipin expression levels distinguish HIV patients with and without lipodystrophy. Int. J. Obes. (Lond.) 31, 449-456. https://doi.org/10.1038/sj.ijo.0803434
  29. Ma, Y. N., Zhang, X., Yu, H. C. and Zhang, J. W. 2010. 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. https://doi.org/10.1186/1471-2121-11-75
  30. Masuda, M., Oshima, A., Noguchi, T. and Kagiwada, S. 2015. Induction of intranuclear membranes by overproduction of Opi1p and Scs2p, regulators for yeast phospholipid biosynthesis, suggests a mechanism for Opi1p nuclear translocation. J. Biochem. 159, 351-361.
  31. Mayfield, J. E., Burkholder, N. T. and Zhang, Y. J. 2016. Dephosphorylating eukaryotic RNA polymerase II. Biochim. Biophys. Acta 1864, 372-387. https://doi.org/10.1016/j.bbapap.2016.01.007
  32. Mayfield, J. E., Fan, S., Wei, S., Zhang, M., Li, B. and Ellington, A. D., et al. 2015. Chemical tools to decipher regulation of phosphatases by proline isomerization on eukaryotic RNA polymerase II. ACS Chem. Biol. 10, 2405-2414. https://doi.org/10.1021/acschembio.5b00296
  33. Meinhart, A., Kamenski, T., Hoeppner, S., Baumli, S. and Cramer, P. 2005. A structural perspective of CTD function. Genes Dev. 19, 1401-1415. https://doi.org/10.1101/gad.1318105
  34. Mul, J. D., Nadra, K., Jagalur, N. B., Nijman, I. J., Toonen, P. W. and Medard, J. J., et al. 2011. A hypomorphic mutation in Lpin1 induces progressively improving neuropathy and lipodystrophy in the rat. J. Biol. Chem. 286, 26781-26793. https://doi.org/10.1074/jbc.M110.197947
  35. Mustelin, T. 2007. A brief introduction to the protein phosphatase families. Methods Mol. Biol. 365, 9-22.
  36. Nesti, E., Corson, G. M., McCleskey, M., Oyer, J. A. and Mandel, G. 2014. C-terminal domain small phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation. Proc. Natl. Acad. Sci. USA 111, E3929-3936. https://doi.org/10.1073/pnas.1414770111
  37. Notredame, C., Higgins, D. G. and Heringa, J. 2000. T-Coffee: A novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 302, 205-217. https://doi.org/10.1006/jmbi.2000.4042
  38. O'Hara, L., Han, G. S., Peak-Chew, S., Grimsey, N., Carman, G. M. and Siniossoglou, S. 2006. Control of phospholipid synthesis by phosphorylation of the yeast lipin Pah1p/Smp2p Mg2+-dependent phosphatidate phosphatase. J. Biol. Chem. 281, 34537-34548. https://doi.org/10.1074/jbc.M606654200
  39. Payne, V. A., Grimsey, N., Tuthill, A., Virtue, S., Gray, S. L. and Dalla Nora, E., et al. 2008. The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiation. Diabetes 57, 2055-2060. https://doi.org/10.2337/db08-0184
  40. Peterfy, M., Phan, J., Xu, P. and Reue, K. 2001. Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nat. Genet. 27, 121-124. https://doi.org/10.1038/83685
  41. Phan, J. and Reue, K. 2005. Lipin, a lipodystrophy and obesity gene. Cell Metab. 1, 73-83. https://doi.org/10.1016/j.cmet.2004.12.002
  42. R, H. R., Kim, H., Noh, K. and Kim, Y. J. 2014. The diverse roles of RNA polymerase II C-terminal domain phosphatase SCP1. BMB Rep. 47, 192-196. https://doi.org/10.5483/BMBRep.2014.47.4.060
  43. Rosonina, E. and Blencowe, B. J. 2004. Analysis of the requirement for RNA polymerase II CTD heptapeptide repeats in pre-mRNA splicing and 3'-end cleavage. RNA 10, 581-589. https://doi.org/10.1261/rna.5207204
  44. Sakaguchi, M., Sharmin, S., Taguchi, A., Ohmori, T., Fujimura, S. and Abe, T., et al. 2013. The phosphatase Dullard negatively regulates BMP signalling and is essential for nephron maintenance after birth. Nat. Commun. 4, 1398. https://doi.org/10.1038/ncomms2408
  45. Santos-Rosa, H., Leung, J., Grimsey, N., Peak-Chew, S. and Siniossoglou, S. 2005. The yeast lipin Smp2 couples phospholipid biosynthesis to nuclear membrane growth. EMBO J. 24, 1931-1941. https://doi.org/10.1038/sj.emboj.7600672
  46. Sapkota, G., Knockaert, M., Alarcon, C., Montalvo, E., Brivanlou, A. H. and Massague, J. 2006. Dephosphorylation of the linker regions of Smad1 and Smad2/3 by small C-terminal domain phosphatases has distinct outcomes for bone morphogenetic protein and transforming growth factor-beta pathways. J. Biol. Chem. 281, 40412-40419. https://doi.org/10.1074/jbc.M610172200
  47. Satow, R., Chan, T. C. and Asashima, M. 2002. Molecular cloning and characterization of dullard: a novel gene required for neural development. Biochem. Biophys. Res. Commun. 295, 85-91. https://doi.org/10.1016/S0006-291X(02)00641-1
  48. Senchenko, V. N., Anedchenko, E. A., Kondratieva, T. T., Krasnov, G. S., Dmitriev, A. A. and Zabarovska, V. I., et al. 2010. Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer. BMC Cancer 10, 75. https://doi.org/10.1186/1471-2407-10-75
  49. Shi, Y. 2009. Serine/threonine phosphatases: mechanism through structure. Cell 139, 468-484. https://doi.org/10.1016/j.cell.2009.10.006
  50. Sim, M. F., Dennis, R. J., Aubry, E. M., Ramanathan, N., Sembongi, H. and Saudek, V., et al. 2012. The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 1. Mol. Metab. 2, 38-46.
  51. Sim, M. F., Talukder, M. M., Dennis, R. J., O'Rahilly, S., Edwardson, J. M. and Rochford, J. J. 2013. Analysis of naturally occurring mutations in the human lipodystrophy protein seipin reveals multiple potential pathogenic mechanisms. Diabetologia 56, 2498-2506. https://doi.org/10.1007/s00125-013-3029-3
  52. Sim, M. F., Talukder, M. U., Dennis, R. J., Edwardson, J. M. and Rochford, J. J. 2014. Analyzing the functions and structure of the human lipodystrophy protein seipin. Methods Enzymol. 537, 161-175.
  53. Sinha, S., Singh, R. K., Alam, N., Roy, A., Roychoudhury, S. and Panda, C. K. 2008. Frequent alterations of hMLH1 and RBSP3/HYA22 at chromosomal 3p22.3 region in early and late-onset breast carcinoma: clinical and prognostic significance. Cancer Sci. 99, 1984-1991.
  54. Son, S. and Osmani, S. A. 2009. Analysis of all protein phosphatase genes in Aspergillus nidulans identifies a new mitotic regulator, fcp1. Eukaryot. Cell 8, 573-585. https://doi.org/10.1128/EC.00346-08
  55. Su, Y. A., Lee, M. M., Hutter, C. M. and Meltzer, P. S. 1997. Characterization of a highly conserved gene (OS4) amplified with CDK4 in human sarcomas. Oncogene 15, 1289-1294. https://doi.org/10.1038/sj.onc.1201294
  56. Suh, M. H., Ye, P., Zhang, M., Hausmann, S., Shuman, S., Gnatt, A. L. and Fu, J. 2005. Fcp1 directly recognizes the C-terminal domain (CTD) and interacts with a site on RNA polymerase II distinct from the CTD. Proc. Natl. Acad. Sci. USA 102, 17314-17319. https://doi.org/10.1073/pnas.0507987102
  57. Sun, G., Hu, Z., Min, Z., Yan, X., Guan, Z. and Su, H., et al. 2015. Small C-terminal Domain Phosphatase 3 Dephosphorylates the Linker Sites of Receptor-regulated Smads (R-Smads) to Ensure Transforming Growth Factor beta (TGFbeta)-mediated Germ Layer Induction in Xenopus Embryos. J. Biol. Chem. 290, 17239-17249. https://doi.org/10.1074/jbc.M115.655605
  58. Szymanski, K. M., Binns, D., Bartz, R., Grishin, N. V., Li, W. P. and Agarwal, A. K., et al. 2007. The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology. Proc. Natl. Acad. Sci. USA 104, 20890-20895. https://doi.org/10.1073/pnas.0704154104
  59. Tanaka, S. S., Nakane, A., Yamaguchi, Y. L., Terabayashi, T., Abe, T. and Nakao, K., et al. 2013. Dullard/Ctdnep1 modulates WNT signalling activity for the formation of primordial germ cells in the mouse embryo. PLoS One 8, e57428. https://doi.org/10.1371/journal.pone.0057428
  60. Thompson, J., Lepikhova, T., Teixido-Travesa, N., Whitehead, M. A., Palvimo, J. J. and Janne, O. A. 2006. Small carboxyl-terminal domain phosphatase 2 attenuates androgen-dependent transcription. EMBO J. 25, 2757-2767. https://doi.org/10.1038/sj.emboj.7601161
  61. Urrutia, H., Aleman, A. and Eivers, E. 2016. Drosophila Dullard functions as a Mad phosphatase to terminate BMP signaling. Sci. Rep. 6, 32269. https://doi.org/10.1038/srep32269
  62. Varon, R., Gooding, R., Steglich, C., Marns, L., Tang, H. and Angelicheva, D., et al. 2003. Partial deficiency of the C-terminal-domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome. Nat. Genet. 35, 185-189. https://doi.org/10.1038/ng1243
  63. Visconti, R., Della Monica, R., Palazzo, L., D'Alessio, F., Raia, M. and Improta, S., et al. The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs. Cell Death Differ. 22, 1551-1560. https://doi.org/10.1038/cdd.2015.13
  64. Visconti, R., Palazzo, L., Della Monica, R. and Grieco, D. 2012. Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit. Nat. Commun. 3, 894. https://doi.org/10.1038/ncomms1886
  65. Wang, W., Liao, P., Shen ,M., Chen, T., Chen, Y. and Li, Y., et al. 2015. SCP1 regulates c-Myc stability and functions through dephosphorylating c-Myc Ser62. Oncogene 35, 491-500.
  66. Wani, S., Sugita, A., Ohkuma, Y. and Hirose, Y. 2016. Human SCP4 is a chromatin-associated CTD phosphatase and exhibits the dynamic translocation during erythroid differentiation. J. Biochem. 160, 111-120. https://doi.org/10.1093/jb/mvw018
  67. Wee, K., Yang, W., Sugii, S. and Han, W. 2014. Towards a mechanistic understanding of lipodystrophy and seipin functions. Biosci. Rep. 34, e00141
  68. Witkin, K. L., Friederichs, J. M., Cohen-Fix, O. and Jaspersen, S. L. 2010 Changes in the nuclear envelope environment affect spindle pole body duplication in Saccharomyces cerevisiae. Genetics 186, 867-883. https://doi.org/10.1534/genetics.110.119149
  69. Wolinski, H., Hofbauer, H. F., Hellauer, K., Cristobal-Sarramian, A., Kolb, D. and Radulovic, M., et al. 2015. Seipin is involved in the regulation of phosphatidic acid metabolism at a subdomain of the nuclear envelope in yeast. Biochim. Biophys. Acta 1851, 1450-1464. https://doi.org/10.1016/j.bbalip.2015.08.003
  70. Wrighton, K. H., Willis, D., Long, J., Liu, F., Lin, X. and Feng, X. H. 2006. Small C-terminal domain phosphatases dephosphorylate the regulatory linker regions of Smad2 and Smad3 to enhance transforming growth factor-beta signaling. J. Biol. Chem. 281, 38365-38375. https://doi.org/10.1074/jbc.M607246200
  71. Yeo, M., Lee, S. K., Lee, B., Ruiz, E. C., Pfaff, S. L. and Gill, G. N. 2005. Small CTD phosphatases function in silencing neuronal gene expression. Science 307, 596-600. https://doi.org/10.1126/science.1100801
  72. Yeo, M. and Lin, P. S. 2007. Functional characterization of small CTD phosphatases. Methods Mol. Biol. 365, 335-346.
  73. Yeo, M., Lin, P. S., Dahmus, M. E. and Gill, G. N. 2003. A novel RNA polymerase II C-terminal domain phosphatase that preferentially dephosphorylates serine 5. J. Biol. Chem. 278, 26078-26085. https://doi.org/10.1074/jbc.M301791200
  74. Yun, J. H., Ko, S., Lee, C. K., Cheong, H. K., Cheong, C., Yoon, J. B. and Lee, W. 2013. Solution structure and Rpn1 interaction of the UBL domain of human RNA polymerase II C-terminal domain phosphatase. PLoS One 8, e62981. https://doi.org/10.1371/journal.pone.0062981
  75. Zhang, D. W., Mosley, A. L., Ramisetty, S. R., Rodriguez-Molina, J. B., Washburn, M. P. and Ansari, A. Z. 2012. Ssu72 phosphatase-dependent erasure of phospho-Ser7 marks on the RNA polymerase II C-terminal domain is essential for viability and transcription termination. J. Biol. Chem. 287, 8541-8551. https://doi.org/10.1074/jbc.M111.335687
  76. Zhang, M., Cho, E. J., Burstein, G., Siegel, D. and Zhang, Y. 2011. Selective inactivation of a human neuronal silencing phosphatase by a small molecule inhibitor. ACS Chem. Biol. 6, 511-519. https://doi.org/10.1021/cb100357t
  77. Zhang, M., Liu J., Kim, Y., Dixon, J. E., Pfaff, S. L. and Gill, G. N., et al. 2010. Structural and functional analysis of the phosphoryl transfer reaction mediated by the human small C-terminal domain phosphatase, Scp1. Protein Sci. 19, 974-986.
  78. Zhang, Y., Kim, Y., Genoud, N., Gao, J., Kelly, J. W. and Pfaff, S. L., et al. 2006. Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1. Mol. Cell 24, 759-770. https://doi.org/10.1016/j.molcel.2006.10.027
  79. Zhao, Y., Xiao, M., Sun, B., Zhang, Z., Shen, T. and Duan, X., et al. 2014. C-terminal domain (CTD) small phosphatase-like 2 modulates the canonical bone morphogenetic protein (BMP) signaling and mesenchymal differentiation via Smad dephosphorylation. J. Biol. Chem. 289, 26441-26450. https://doi.org/10.1074/jbc.M114.568964
  80. Zheng, H., Ji, C., Gu, S., Shi, B., Wang, J., Xie, Y. and Mao, Y. 2005. Cloning and characterization of a novel RNA polymerase II C-terminal domain phosphatase. Biochem. Biophys. Res. Commun. 331, 1401-1407. https://doi.org/10.1016/j.bbrc.2005.04.065
  81. Zhong, R., Ge, X., Chu, T., Teng, J., Yan, B. and Pei, J., et al. 2015. Lentivirus-mediated knockdown of CTDP1 inhibits lung cancer cell growth in vitro. J. Cancer Res. Clin. Oncol. 142, 723-732.
  82. Zohn, I. E. and Brivanlou, A. H. 2001. Expression cloning of Xenopus Os4, an evolutionarily conserved gene, which induces mesoderm and dorsal axis. Dev. Biol. 239, 118-131. https://doi.org/10.1006/dbio.2001.0420