Carboxy-terminal domain phosphatase 1 silencing results in the inhibition of tumor formation ability in gastric cancer cells

Fu, Hongbing; Yang, Dejun; Wang, Changming; Xu, Jiapeng; Wang, Weimin; Yan, Ran; Cai, Qing-Qing

doi:10.3892/ol.2015.3693

Cited by 3 publications

(2 citation statements)

References 17 publications

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“…S8B). CTDP1 depletion in vitro and in vivo diminishes tumorigenic potential of breast cancer models, which is also consistent with previous findings in gastric and lung cancer in vitro experiments 46,47 . These data suggest that CTDP1 could be a promising target for cancer therapeutic development.…”

Section: Resultssupporting

confidence: 92%

CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific interactions with FANCI

Krieger

Lagundžin

et al. 2019

Cell Death Discov.

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BRCA1 C-terminal domains are found in a specialized group of 23 proteins that function in the DNA damage response to protect genomic integrity. C-terminal domain phosphatase 1 (CTDP1) is the only phosphatase with a BRCA1 C-terminal domain in the human proteome, yet direct participation in the DNA damage response has not been reported. Examination of the CTDP1 BRCA1 C-terminal domain-specific protein interaction network revealed 103 high confidence interactions enriched in DNA damage response proteins, including FANCA and FANCI that are central to the Fanconi anemia DNA repair pathway necessary for the resolution of DNA interstrand crosslink damage. CTDP1 expression promotes DNA damage-induced FANCA and FANCD2 foci formation and enhances homologous recombination repair efficiency. CTDP1 was found to regulate multiple aspects of FANCI activity, including chromatin localization, interaction with γ-H2AX, and SQ motif phosphorylations. Knockdown of CTDP1 increases MCF-10A sensitivity to DNA interstrand crosslinks and double-strand breaks, but not ultraviolet radiation. In addition, CTDP1 knockdown impairs in vitro and in vivo growth of breast cancer cell lines. These results elucidate the molecular functions of CTDP1 in Fanconi anemia interstrand crosslink repair and identify this protein as a potential target for breast cancer therapy.

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Section: Resultssupporting

confidence: 92%

CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific interactions with FANCI

Krieger

Lagundžin

et al. 2019

Cell Death Discov.

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“…CCFDN is caused by the splicing variant IVS6+389C>T in intron 6 of CTDP1, leading to the production of 30% functional CTDP1 protein and 70% truncated protein (Varon et al, 2003;Kalaydjieva, 2006). In addition, there is emerging evidence of an association between CTDP1 and cancer (Fu et al, 2015;Zhong et al, 2016). Indeed, a recent study by our lab found that CTDP1 knockdown not only increases the sensitivity of breast cell lines to DNA inter-strand crosslink (ICL)-inducing agents but also compromises the growth of breast cancer cells in vitro and in vivo (Hu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Ctdp1 deficiency leads to early embryonic lethality in mice and defects in cell cycle progression in MEFs

et al. 2021

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RNA polymerase II subunit A Carboxy-Terminal Domain Phosphatase 1 (CTDP1), a member of the haloacid dehalogenase superfamily phosphatases, has a defined role in transcriptional regulation, but emerging evidence suggests an expanded functional repertoire in the cell cycle and DNA damage response. In humans, a splice site mutation in CTDP1 gives rise to the rare Congenital Cataracts Facial Dysmorphism and Neuropathy syndrome, and recent evidence from our lab indicates CTDP1 is required for breast cancer growth and proliferation. To explore the physiological function of CTDP1 in a mammalian system, we generated a conditional Ctdp1 knockout mouse model by insertion of loxP sites upstream of exon 3 and downstream of exon 4. Biallelic deletion of Ctdp1 results in lethality before embryonic day 7.5, with morphological features indicating embryo cell death and resorption. However, Ctdp1+/− mice are haplosufficient for phenotypic traits including body weight, hematological parameters, exploratory and locomotive functions. To investigate the potential mechanisms of the embryonic death caused by biallelic Ctdp1 knockout, mouse embryonic fibroblasts (MEFs) were established from Ctdp1+/+ and Ctdp1flox/flox mice. Lentivirus delivered Cre-mediated biallelic deletion of Ctdp1 in MEFs results in cell death preceded by impaired proliferation characterized by an increase in G1- and G2-phase populations and a reduction in the S-phase population. These cell cycle alterations caused by deletion of Ctdp1 are associated with an increase in p27 protein expression and a decrease in phosphorylated RB, phosphorylated Histone H3, and Cyclin B expression. Together, these results reveal that Ctdp1 plays an essential role in early mouse embryo development and cell growth and survival in part by regulating the cell cycle.

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Emerging Roles of CTD Phosphatases

Kim¹

2017

Journal of Life Science

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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.

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Carboxy-terminal domain phosphatase 1 silencing results in the inhibition of tumor formation ability in gastric cancer cells

Cited by 3 publications

References 17 publications

CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific interactions with FANCI

CTDP1 regulates breast cancer survival and DNA repair through BRCT-specific interactions with FANCI

Ctdp1 deficiency leads to early embryonic lethality in mice and defects in cell cycle progression in MEFs

Emerging Roles of CTD Phosphatases

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