CLSPN

Last update 08 May 2025

Basic Info

Synonyms

claspin, CLSPN, hClaspin

Introduction

Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717).

100 Clinical Results associated with CLSPN

100 Translational Medicine associated with CLSPN

0 Patents (Medical) associated with CLSPN

256

Literatures (Medical) associated with CLSPN

31 Dec 2024·Human Vaccines & Immunotherapeutics

Establishment of potent TCR-T cells specific for cisplatin-resistance related tumor-associated antigen, CLSPN using codon-optimization

Article

Author: Morita, Rena ; Sasaki, Kenta ; Abe, Takashige ; Yamada, Shuhei ; Minowa, Tomoyuki ; Tokita, Serina ; Torigoe, Toshihiko ; Murata, Kenji ; Tsukahara, Tomohide ; Kanaseki, Takayuki ; Hirohashi, Yoshihiko ; Murai, Aiko ; Mizue, Yuka ; Hori, Kanta ; Shijubou, Naoki ; Kubo, Terufumi ; Shinohara, Nobuo ; Miyata, Haruka

Adoptive T cell therapy, using T cell receptor-engineered T (TCR-T) cells and chimeric antigen receptor T (CAR-T) cells, is a potent immunotherapy option. Bladder cancer is a prevalent urological malignancy, particularly in cases of muscle invasion and metastasis, for which systemic therapy is crucial. Immunotherapy utilizing immune checkpoint blockade has been approved for bladder cancer treatment. The antitumor effect of an immune checkpoint blockade based on cytotoxic T cells (CTLs) and the patient's immune status is essential. The chemotherapeutic drug cisplatin (CDDP) is a key drug in bladder cancer treatment. However, it has been shown to suppress T cells, making combination therapy with CDDP and immunotherapy difficult. To address this, we developed TCR-T cells specific for bladder cancer cells. In previous studies, we found that the tumor-associated antigen CLSPN is overexpressed in CDDP-resistant bladder cancer cells and that the antigenic peptide HLA-A*02:01/CLSPN_1254-1262, encoded by CLSPN, could be targeted by a CTL clone. The TCR was cloned from the HLA-A*02:01/CLSPN_1254-1262 specific CTL clone yc3. We also designed a codon-optimized TCR sequence using GeneArt® GeneOptimizer® (Opt TCR) and compared the TCR-T cells using the original TCR sequence (Ori TCR-T cells) and the codon-optimized TCR sequence (Opt TCR-T cells). Opt TCR-T cells exhibited higher TCR transduction efficiency, higher TCR expression levels, higher avidity, and greater cytotoxicity than did Ori TCR-T cells. These results suggest that HLA-A*02:01/CLSPN_1254-1262 specific Opt TCR-T cells are promising candidates for CDDP combination therapy.

01 Dec 2024·Molecular and Cellular Neuroscience

Inhibition of phosphodiesterase 10A mitigates neuronal injury by modulating apoptotic pathways in cold-induced traumatic brain injury

Article

Author: Dogan, Enes ; Kilic, Ertugrul ; Beker, Mustafa C ; Balaban, Buse ; Altintas, Mehmet O ; Beker, Mustafa C. ; Ozpinar, Aysenur ; Sengun, Nursena ; Bayraktaroglu, Cigdem ; Altunay, Serdar ; Altintas, Mehmet O.

Brain injury develops from a complex series of pathophysiological phases, resulting in acute necrotic or delayed apoptotic cell death after traumatic brain injury (TBI). Inhibition of apoptotic cell death is critical for the treatment of acute neurodegenerative disorders, such as TBI. Here, we investigated the role of phosphodiesterase 10A (PDE10A) in the development of neuronal injury, particularly in apoptotic cell death. Using the PDE10A inhibitor TAK-063, we found that PDE10A inhibition is associated with decreased brain injury, brain swelling, and blood brain barrier disruption 48 h after cold-induced TBI. Furthermore, a particularly notable result was observed with 3 mg/kg TAK-063, which reduced disseminated neuronal injury. Protein abundance analysis revealed that PDE10A inhibition activates survival kinases AKT and ERK-1/-2, which were associated with the decreased activation of MMP-9 and PTEN. Additionally, iNOS and nNOS levels significantly reduced in the TAK-063 group, playing roles in inflammation and apoptosis. A planar surface immunoassay was performed for in-depth analyses of the apoptotic signaling pathways. We observed that inhibition of PDE10A resulted in the decreased expression of TNFRSF1A, TNFRSF10B, and TNFRSF6 receptors, particularly inducing apoptotic cell death. Moreover, these findings correlated with reduced levels of pro-apoptotic proteins, including PTEN, p27, Cytochrome-c, cleaved Caspase-3, Bad, and p53. Interestingly, TAK-063 treatment reduced levels of anti-apoptotic proteins or enzymes, including XIAP, Claspin, and HIF1α, without affecting Bcl-x, MCL-1, SMAC, HO-1, HO-2, HSP27, HSP60, and HSP70. The findings suggest that PDE10A regulates cellular signaling predominantly pro-apoptotic pathways, and inhibition of this protein is a promising approach for the treatment of acute brain injury.

01 Dec 2024·Environmental Toxicology

Picrasidine I Regulates Apoptosis in Melanoma Cell Lines by Activating ERK and JNK Pathways and Suppressing AKT Signaling

Article

Author: Hsieh, Ming‐Ju ; Lin, Chia‐Chieh ; Lo, Yu‐Sheng ; Ho, Hsin‐Yu ; Shieu, Mu‐Kuei ; Chuang, Yi‐Ching

ABSTRACTWorld Health Organization data indicate a continuous increase in melanoma incidence, with metastatic melanoma characterized by poor prognosis and drug resistance. The exploration of therapeutics derived from natural products remains an active area of in vitro research. The aim of this study was to determine the antitumor effects of picrasidine I, a natural compound extracted from Picrasma quassioides, against two melanoma cell lines. We selected two metastatic melanoma cell lines, HMY‐1 and A2058, for molecular studies, including Western blotting, 4′,6‐diamidino‐2‐phenylindole staining, and flow cytometry. Picrasidine I demonstrated cytotoxic effects against the HMY‐1 and A2058 melanoma cell lines. It induced cell cycle arrest in the sub‐G1 phase and downregulated cell cycle–related proteins (e.g., cyclin A2, D1, cyclin‐dependent kinases 4, and 6). In the intrinsic apoptosis pathway, picrasidine I activated proapoptotic proteins (e.g., Bax, Bak, t‐Bid, BimL/S) and suppressed the expression of antiapoptotic proteins (e.g., Bcl‐2, Bcl‐xL), with an observed increase in the quantity of depolarized cells. In addition, the apoptotic effects of picrasidine I were linked to the activation of the c‐Jun N‐terminal kinase and extracellular signal‐regulated kinase pathways and the inhibition of the protein kinase B signaling pathway. A human apoptosis array indicated claspin inhibition upon picrasidine I treatment, suggesting the potential involvement of picrasidine I in apoptosis and cell cycle regulation. Our findings suggest that picrasidine I has potential as a candidate for treating advanced melanoma, and thus these findings warrant further investigation. The modulation of claspin expression by picrasidine I could be investigated further as a potential biomarker to predict its efficacy in related to advanced stages of melanoma.

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CLSPN

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