Last update 01 Nov 2024

NUF2

Last update 01 Nov 2024

Basic Info

Synonyms

CDCA1, Cell division cycle-associated protein 1, CT106

+ [7]

Introduction

Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:12438418, PubMed:14654001, PubMed:15062103, PubMed:15235793, PubMed:15239953, PubMed:15548592, PubMed:17535814). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:15548592). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020).

Drugs associated with NUF2

Asudemotide

Target

DEPDC1 x IGF2BP3 x KIF20B x LY6K x NUF2

Mechanism

DEPDC1 inhibitors [+4]

Active Org.

OncoTherapy Science, Inc. [+1]

Originator Org.

OncoTherapy Science, Inc.

Active Indication

Esophageal Carcinoma [+2]

Inactive Indication-

Drug Highest PhasePhase 3

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

S-588210

Target

IGF2BP3 x LY6K x NUF2

Mechanism

IGF2BP3 agonists [+3]

Active Org.

OncoTherapy Science, Inc. [+1]

Originator Org.

OncoTherapy Science, Inc.

Active Indication

Mesothelioma

Inactive Indication

Bladder Cancer [+4]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with NUF2

NCT04106115 / RecruitingPhase 1/2IIT

A Phase Ib/II Study to Assess the Safety and Activity of DURvalumab (MEDI4736) in Combination With S-488210/S-488211 vAccine in Non-muscle Invasive Bladder CancEr

DURANCE is a two part, phase Ib/II, multi-centre study to assess the safety and activity of S-488210/S-488211 in combination with durvalumab, in patients with non-muscle invasive bladder cancer (NMIBC).

Start Date25 Mar 2022

Sponsor / Collaborator

University College London

[+2]

NCT04316689 / CompletedPhase 1

Open-label, Phase 1 Study of S-488210/S-488211 to Evaluate the Safety and Tolerability in Patients With Unresectable Recurrent and/or Metastatic Solid Tumor

The primary objective is to evaluate the safety and tolerability of S-588210 (S-488210+S-488211) in patients with unresectable recurrent and/or metastatic solid tumors.

Start Date30 Jul 2019

Sponsor / Collaborator

Shionogi, Inc.

JPRN-UMIN000023324 / CompletedPhase 1

Exploratory study to determine S-588410-induced tumor infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients - Exploratory study to determine S-588410-induced tumor infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients

Start Date25 Jul 2016

Sponsor / Collaborator

Shionogi & Co., Ltd.

100 Clinical Results associated with NUF2

100 Translational Medicine associated with NUF2

0 Patents (Medical) associated with NUF2

211

Literatures (Medical) associated with NUF2

01 Nov 2024·Gene

Elevated expression of ECT2 as a diagnostic marker and prognostic indicator in endometrial cancer

Article

Author: Wu, Xiang-Guang ; Huang, Si-Yuan ; Chen, Jin-Jiao ; Wang, Wei ; Zhou, Xiao-Xia ; Fan, Liang-Sheng ; Ding, Zi-Ang ; Qiu, Yang-Zhi ; Pan, Yu-Hua ; Zhong, Xiao-Qing ; Wu, Yu

OBJECTIVESThe study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection.METHODSDifferentially expressed genes (DEGs), Series test of cluster (STC) and protein-protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential.RESULTSUpregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis.CONCLUSIONSECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.

20 Oct 2024·Chinese Medical Journal

Targeting NUF2 suppresses gastric cancer progression through G2/M phase arrest and apoptosis induction

Article

Author: Long, Bo ; Zhang, Boya ; He, Na ; Li, Jian ; Jiao, Zuoyi ; Xin, Wei ; Jiang, Xiangyan ; Yu, Zeyuan ; Zhu, Xiaoqin ; Xiao, Lixia ; Zhou, Huinian ; Ma, Zhijian

AbstractBackground:Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression.Methods:Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC.Results:NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models.Conclusions:Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

20 Sep 2024·Science (New York, N.Y.)

Artificial kinetochore beads establish a biorientation-like state in the spindle.

Article

Author: Kitajima, Tomoya S ; Asai, Kohei ; Zhou, Yuanzhuo ; Takenouchi, Osamu

Faithful chromosome segregation requires biorientation, where the pair of kinetochores on the chromosome establish bipolar microtubule attachment. The integrity of the kinetochore, a macromolecular complex built on centromeric DNA, is required for biorientation, but components sufficient for biorientation remain unknown. Here, we show that tethering the outer kinetochore heterodimer NDC80-NUF2 to the surface of apolar microbeads establishes their biorientation-like state in mouse cells. NDC80-NUF2 microbeads align at the spindle equator and self-correct alignment errors. The alignment is associated with stable bipolar microtubule attachment and is independent of the outer kinetochore proteins SPC24-SPC25, KNL1, the Mis12 complex, inner kinetochore proteins, and Aurora. Larger microbeads align more rapidly, suggesting a size-dependent biorientation mechanism. This study demonstrates a biohybrid kinetochore design for synthetic biorientation of microscale particles in cells.

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