Targeting the C-Terminal Domain Small Phosphatase 1

Rallabandi, Harikrishna Reddy; Ganesan, Palanivel; Kim, Young Jun

doi:10.3390/life10050057

Cited by 14 publications

(13 citation statements)

References 154 publications

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“…We found that hsa-let-7b_5c acquired 292 additional targets, including VBP1 and CTDSP1. Recently, some studies demonstrated that CTDSP1 inhibited the proliferation, migration and invasion of cancer cells by inhibiting the dephosphorylation of TWIST and AKT, suggesting a tumor suppressor role of CTDSP1 ( Rallabandi et al, 2020 ; Yang X. et al, 2021 ). Furthermore, a study showed the role of CTDSP1 in cell cycle arrest during the G1/S transition through c-Myc-mediated dephosphorylation of retinoblastoma protein (RB) ( Liu et al, 2016 ; Wang et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNA editing sites in three subtypes of leukemia

Xie

Yang²,

Zhou

et al. 2022

Front. Mol. Biosci.

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Leukemia is an aberrant hyper-proliferation of immature blood cells that do not form solid tumors. The transcriptomes of microRNAs (miRNAs) of leukemia have been intensively explored. However, miRNA editing of leukemia has not been extensively studied. To identify miRNA editing patterns and explore their functional relevance in leukemia, we analyzed 200 small RNA sequencing profiles of three subtypes of leukemia and identified hundreds of miRNA editing sites in three subtypes of leukemia. Then, we compared the editing levels of identified miRNA editing sites in leukemia and normal controls. Many miRNAs were differential edited in different subtypes of leukemia. We also found the editing levels of 3′-A editing sites of hsa-mir-21-5p and hsa-mir-155-5p decreased in chronic lymphocytic leukemia patients with radiation treatments. By integrating PAR-CLIP sequencing profiles, we predicted the targets of original and edited miRNAs. One of the edited miRNA, hsa-let-7b_5c, with an additional cytosine at 5′ end of hsa-let-7b-5p, potentially targeted VBP1 and CTDSP1. CTDSP1 was significantly downregulated in T-ALL compared to normal controls, which might be originated from the hyperediting of hsa-let-7b-5p in T-ALL. Our study provides a comprehensive view of miRNA editing in three different subtypes of leukemia.

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Section: Discussionmentioning

confidence: 99%

Identification of microRNA editing sites in three subtypes of leukemia

Xie

Yang²,

Zhou

et al. 2022

Front. Mol. Biosci.

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“…The HAD family of phosphatases or hydrolases have a wide spectrum of substrates that includes proteins, lipids, small molecules, and metabolites [77] (Table 2). Multiple sequence alignment and phylogenetic analysis revealed that trypanosomatid-Tim50 is grouped with Tim50s from other eukaryotes and is distinctly separated from other HAD-family proteins like lipin [75], small CTD-phosphatases (SCP1, FCP1) [78], ubiquitin-like domain containing CTD phosphatase (UBLCP) [79], and Dullard phosphatase [80] (Figure 3). Therefore, it seems TbTim50 is a special kind of HAD phosphatase with both protein-and lipid phosphatase activities and in addition plays role in protein translocation.…”

Section: Tim50 Primary Structure and Membrane Topologymentioning

confidence: 99%

Diverse Functions of Tim50, a Component of the Mitochondrial Inner Membrane Protein Translocase

Chaudhuri

Tripathi

Gonzalez

2021

IJMS

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Mitochondria are essential in eukaryotes. Besides producing 80% of total cellular ATP, mitochondria are involved in various cellular functions such as apoptosis, inflammation, innate immunity, stress tolerance, and Ca2+ homeostasis. Mitochondria are also the site for many critical metabolic pathways and are integrated into the signaling network to maintain cellular homeostasis under stress. Mitochondria require hundreds of proteins to perform all these functions. Since the mitochondrial genome only encodes a handful of proteins, most mitochondrial proteins are imported from the cytosol via receptor/translocase complexes on the mitochondrial outer and inner membranes known as TOMs and TIMs. Many of the subunits of these protein complexes are essential for cell survival in model yeast and other unicellular eukaryotes. Defects in the mitochondrial import machineries are also associated with various metabolic, developmental, and neurodegenerative disorders in multicellular organisms. In addition to their canonical functions, these protein translocases also help maintain mitochondrial structure and dynamics, lipid metabolism, and stress response. This review focuses on the role of Tim50, the receptor component of one of the TIM complexes, in different cellular functions, with an emphasis on the Tim50 homologue in parasitic protozoan Trypanosoma brucei.

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“…Our results show a small, non-statistically significant difference between REST and CTDSP1 knockdown in promoting the expression of BDNF and NGF. This difference may be due to the activity of structural and functional paralogs of CTDSP1, namely CTDSP2 and CTDSPL, which are not affected by CTDSP1 siRNA 33,35,36 .…”

Section: Discussionmentioning

confidence: 99%

C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration in peripheral nerve tissue

Gervasi

Dimtchev

Clark

et al. 2021

Sci Rep

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Peripheral Nerve Injury (PNI) represents a major clinical and economic burden. Despite the ability of peripheral neurons to regenerate their axons after an injury, patients are often left with motor and/or sensory disability and may develop chronic pain. Successful regeneration and target organ reinnervation require comprehensive transcriptional changes in both injured neurons and support cells located at the site of injury. The expression of most of the genes required for axon growth and guidance and for synapsis formation is repressed by a single master transcriptional regulator, the Repressor Element 1 Silencing Transcription factor (REST). Sustained increase of REST levels after injury inhibits axon regeneration and leads to chronic pain. As targeting of transcription factors is challenging, we tested whether modulation of REST activity could be achieved through knockdown of carboxy-terminal domain small phosphatase 1 (CTDSP1), the enzyme that stabilizes REST by preventing its targeting to the proteasome. To test whether knockdown of CTDSP1 promotes neurotrophic factor expression in both support cells located at the site of injury and in peripheral neurons, we transfected mesenchymal progenitor cells (MPCs), a type of support cells that are present at high concentrations at the site of injury, and dorsal root ganglion (DRG) neurons with REST or CTDSP1 specific siRNA. We quantified neurotrophic factor expression by RT-qPCR and Western blot, and brain-derived neurotrophic factor (BDNF) release in the cell culture medium by ELISA, and we measured neurite outgrowth of DRG neurons in culture. Our results show that CTDSP1 knockdown promotes neurotrophic factor expression in both DRG neurons and the support cells MPCs, and promotes DRG neuron regeneration. Therapeutics targeting CTDSP1 activity may, therefore, represent a novel epigenetic strategy to promote peripheral nerve regeneration after PNI by promoting the regenerative program repressed by injury-induced increased levels of REST in both neurons and support cells.

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Targeting the C-Terminal Domain Small Phosphatase 1

Cited by 14 publications

References 154 publications

Identification of microRNA editing sites in three subtypes of leukemia

Identification of microRNA editing sites in three subtypes of leukemia

Diverse Functions of Tim50, a Component of the Mitochondrial Inner Membrane Protein Translocase

C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration in peripheral nerve tissue

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