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Last update 08 May 2025

PTTG1

Last update 08 May 2025

Basic Info

Synonyms

EAP1, Esp1-associated protein, HPTTG

+ [7]

Introduction

Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of TP53. The negative regulation of TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation.

Drugs associated with PTTG1

HG-1005

Target

PTTG1

Mechanism

PTTG1 modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Neoplasms [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PTTG1

100 Translational Medicine associated with PTTG1

0 Patents (Medical) associated with PTTG1

1,159

Literatures (Medical) associated with PTTG1

01 Jun 2025·Phytomedicine

Valproic acid promotes transcriptional activation of Drd2 by mediating histone acetylation to inhibit the mTOR–Pttg1 signaling axis and exerts anti-PitNETs activity

Article

Author: Lin, Yingda ; Feng, Qingling ; Wang, Youwei ; Peng, Aijun ; Du, Qiu ; Li, Yaru ; Chen, Zhiyong ; Feng, Zize ; Xu, Lei

BACKGROUNDValproic acid (VPA), a short branched-chain fatty acid derived from valeric acid naturally produced by Valeriana officinalis L., is widely used in clinical settings for the treatment of epilepsy. Furthermore, VPA has been shown to reduce prolactin (PRL) levels in epileptic patients and exerts anti-tumor properties. Nevertheless, the prospective anti-pituitary neuroendocrine tumors (PitNETs) effects and the underlying mechanism of VPA remain unknown.PURPOSETo assess VPA's efficacy in inhibiting PitNETs cell growth and hormone secretion, and to investigate the underlying mechanisms.STUDY DESIGN/METHODSThe pharmacological effects of VPA in PitNETs cells were assessed using CCK-8, colony formation, EdU staining, cell cycle/apoptosis, cell migration/invasion, and ELISA assays. The relevant VPA targets against PitNETs were assessed via RNA-sequencing and validated by qRT-PCR. CUT&RUN-qPCR was performed to detect the enrichment of DNA fragments precipitated by associated antibodies. Immunohistochemistry and western blot analysis were performed to assess the levels of factors associated with apoptosis, cell cycle, autophagy, and mTOR-Pttg1 signaling pathway activation.RESULTSVPA significantly inhibited the proliferation, invasivity, and PRL secretion of PitNET GH3 cells, induced cytoprotective autophagy, and also inhibited GH3-xenografted tumor growth and PRL secretion in vivo. Pretreatment with the autophagy inhibitor significantly enhanced the inhibitory effects of VPA on GH3 cell growth and PRL secretion, and further promoted VPA-induced apoptosis. RNA sequencing analysis revealed 927 upregulated and 878 downregulated genes in VPA-treated GH3 cells, and the cell cycle and other pathways were significantly enriched. Moreover, several crucial genes, including markers of proliferation Kiel 67 (Mki67), pituitary transforming gene 1 (Pttg1), and dopamine D2 receptor (Drd2), were regulated by VPA. Mechanistically, VPA induced increased histone acetylation at Drd2 promoter, activating its transcription and inhibiting the mechanistic target of the rapamycin (mTOR)-Pttg1 signaling axis. Finally, the therapeutic effects of VPA on multiple PitNET cells were evaluated and confirmed its sensitization effects on first-line therapeutics.CONCLUSIONOur results revealed that VPA exerts anti-PitNET effects by promoting Drd2 transcriptional activation, thereby inhibiting the mTOR-Pttg1 signaling axis, indicating the potential therapeutic utility of VPA in PitNET treatment.

01 May 2025·Journal of Autoimmunity

Exploring the correlation between UVB sensitivity and SLE activity: Insights into UVB-driven pathogenesis in lupus erythematosus

Article

Author: Guo, Yuanning ; Xu, Jinhua ; Chen, Jiamin ; He, Jiayu ; Zhu, Xiaohua

Lupus erythematosus (LE) comprises various autoimmune inflammatory diseases, with significant overlap between cutaneous LE (CLE) and systemic LE (SLE). A key feature of both CLE and SLE is UV photosensitivity, particularly in UV-exposure-related skin inflammation. Despite this, reliable and objective UVB photosensitivity indicators closely correlating with LE activity have yet to be identified, and the underlying cellular and molecular mechanisms linking UVB sensitivity with LE onset and progression remain unclear. We discovered that ultraviolet B minimal erythema dose (UVB-MED), a quantitative photosensitivity measure, is a significant and independent risk factor for SLE activity, demonstrating a negative correlation with SLEDAI (r = -0.58, P < 0.0001). Comprehensive transcriptomic analyses of large-scale CLE and SLE samples (5918 in discovery and 7242 in validation datasets) revealed more pronounced and extensive UVB-response gene dysregulation in skin tissues compared to blood. Additionally, 14 lupus activity-correlated, UVB-response genes (UVBACGs) were identified, including eight type I interferon-stimulated genes (IRF7, ISG20, ISG15, IFI44, IFITM1, MX1, LY6E, OASL) and others (JUN, PTTG1, HLA-F, CAV1, HOPX, RPL3), with dysregulation evident in skin, blood, and affected organs (e.g., kidney and synovium). Immunocytes serve as the primary carriers of this dysregulation. Conventional LE therapies and type I interferon-targeted therapies were found to be associated with these genes and can potentially regulate them, thereby contributing to therapeutic effects. These findings highlight the role of UVB in triggering autoimmune inflammation in the skin, which may subsequently spread to systemic inflammation via immune cells and factors. UVBACGs play a critical role in this process and may serve as targets for precise therapies, providing insight into the link between UVB photosensitivity and LE pathogenesis.

01 Apr 2025·Neurotherapeutics

Transcriptionally distinct malignant neuroblastoma populations show selective response to adavosertib treatment

Article

Author: Juan, Hsueh-Fen ; Li, Albert ; Huang, Hsuan-Cheng ; Hsieh, Chiao-Hui ; Chen, Yi-Xuan ; Tseng, Tzu-Yang

Neuroblastoma is an aggressive childhood cancer that arises from the sympathetic nervous system. Despite advances in treatment, high-risk neuroblastoma remains difficult to manage due to its heterogeneous nature and frequent development of drug resistance. Drug repurposing guided by single-cell analysis presents a promising strategy for identifying new therapeutic options. Here, we aim to characterize high-risk neuroblastoma subpopulations and identify effective repurposed drugs for targeted treatment. We performed single-cell transcriptomic analysis of neuroblastoma samples, integrating bulk RNA-seq data deconvolution with clinical outcomes to define distinct malignant cell states. Using a systematic drug repurposing pipeline, we identified and validated potential therapeutic agents targeting specific high-risk neuroblastoma subpopulations. Single-cell analysis revealed 17 transcriptionally distinct neuroblastoma subpopulations. Survival analysis identified a highly aggressive subpopulation characterized by elevated UBE2C/PTTG1 expression and poor patient outcomes, distinct from a less aggressive subpopulation with favorable prognosis. Drug repurposing screening identified Adavosertib as particularly effective against the aggressive subpopulation, validated using SK-N-DZ cells as a representative model. Mechanistically, Adavosertib suppressed cell proliferation through AKT/mTOR pathway disruption, induced G2/M phase cell cycle arrest, and promoted apoptosis. Further analysis revealed UBE2C and PTTG1 as key molecular drivers of drug resistance, where their overexpression enhanced proliferation, Adavosertib resistance, and cell migration. This study establishes a single-cell-based drug repurposing strategy for high-risk neuroblastoma treatment. Our approach successfully identified Adavosertib as a promising repurposed therapeutic agent for targeting specific high-risk neuroblastoma subpopulations, providing a framework for developing more effective personalized treatment strategies.

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PTTG1

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