更新于：2024-09-19

PELP1

更新于：2024-09-19

基本信息

别名

HMX3、MNAR、Modulator of non-genomic activity of estrogen receptor

+ [4]

简介

Coactivator of estrogen receptor-mediated transcription and a corepressor of other nuclear hormone receptors and sequence-specific transcription factors (PubMed:14963108). Plays a role in estrogen receptor (ER) genomic activity when present in the nuclear compartment by activating the ER target genes in a hormonal stimulation dependent manner. Can facilitate ER non-genomic signaling via SRC and PI3K interaction in the cytosol. Plays a role in E2-mediated cell cycle progression by interacting with RB1. May have important functional implications in ER/growth factor cross-talk. Interacts with several growth factor signaling components including EGFR and HRS. Functions as the key stabilizing component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit. Regulates pre-60S association of the critical remodeling factor MDN1 (PubMed:21326211). May promote tumorigenesis via its interaction with and modulation of several oncogenes including SRC, PI3K, STAT3 and EGFR. Plays a role in cancer cell metastasis via its ability to modulate E2-mediated cytoskeleton changes and cell migration via its interaction with SRC and PI3K.

关联

项与 PELP1 相关的药物

SMIP34

靶点

PELP1 x mTOR

作用机制

PELP1抑制剂 [+1]

在研机构

Uthealth Houston

原研机构

Uthealth Houston

在研适应症

子宫内膜癌

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PELP1 相关的临床结果

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100 项与 PELP1 相关的转化医学

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0 项与 PELP1 相关的专利（医药）

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171

项与 PELP1 相关的文献（医药）

2023-10-23·Urology journal

Integrative Analysis of Androgen Receptor Interactors Aberrations and Associated Prognostic Significance in Prostate Cancer.

Article

作者: Wang, Xisheng ; Zhang, Ying ; Wang, Zhu ; Liang, Hui ; Deng, Qiong ; Zhang, Jianwen

PURPOSEMuch progress has been made by directing against the adrogen receptor (AR) pathway in the treatment of prostate cancer in past decades. However, AR-interactors related metastatic castration resistant prostate cancer eventually developed. Here, we aimed to characterize the aberrations and therapeutic implication in advanced disease.MATERIALS AND METHODSSTRING database, UALCAN web portal and cBioPortal platform was used to analyze the AR interaction network, gene alterations, as well as the prognostic significance. GO and KEEG analysis was performed to characterize the functional enrichment of the identified AR-interactors.RESULTSTen first shell AR-interactors were identified, among of which FOXA1 and PELP1 was significantly up-regulated, while CCND1, CTNNB1, NCOA4 and HSP90AA1 exhibited a significantly decreased pattern. The median survival period of altered group (n = 227) was 70 months (95% CI, 60-105M), while that of non-altered group (n = 545) was 141 months (95% CI, 115.13-NA, P < 0.001). GO and KEGG enrichment showed that the identified AR-interactors were particularly enriched in prostate cancer and thyroid hormone signaling pathway, as well as endocrine resistance.CONCLUSIONThe AR-interactors might be useful markers for prostate cancer diagnosis and prognosis, and provide a new sight for revealing the molecular mechanism of CRPC progression.

2023-08-01·International Immunopharmacology

MiR-195-5p is involved in testicular ischemia/reperfusion injury by directly targeting PELP1 and regulating spermatogonia pyroptosis

Article

作者: Xu, Lizhe ; Cheng, Fan ; He, Kai-Xiang ; Ning, Jin-Zhuo

BACKGROUND AND OBJECTIVEIschemia/reperfusion injury (IRI), which is characterized by testicular torsion and causes permanent impairment of spermatogenic function, is linked with pyroptosis. Studies have implicated endogenous small non-coding RNAs in IRI development across various organs. In this study, we elucidated the mechanism underlying miR-195-5p's action in regulating pyroptosis in testicular IRI.METHODSWe established two models, namely a testicular torsion/ detorsion (T/D) mouse model and an oxygen-glucose deprivation/reperfusion (OGD/R)-treated germ cell model. Hematoxylin and eosin staining was performed to evaluate the testicular ischemic injury. The expression of pyroptosis-related proteins and reactive oxygen species production in testis tissues were detected using Western blotting, quantitative real-time PCR, malondialdehyde and superoxide dismutase assay kits and immunohistochemistry. Cell viability and cytotoxicity were evaluated using CCK-8 and LDH assays, whereas expression patterns of inflammatory proteins were measured using ELISA, immunofluorescence, and western blot assays. miR-195-5p interaction with PELP1 was validated by conducting the luciferase enzyme reporter test.RESULTSPyroptosis-related proteins NLRP3, GSDMD, IL-1β, and IL-18 were significantly upregulated following testicular IRI. A similar pattern was observed in the OGD/R model. miR-195-5p was significantly downregulated in mouse IRI testis tissue and OGD/R-treated GC-1 cells. Notably, miR-195-5p downregulation promoted whereas its upregulation attenuated pyroptosis in OGD/R-treated GC-1 cells. Furthermore, we found that PELP1 is a miR-195-5p target. miR-195-5p attenuated pyroptosis in GC-1 cells by inhibiting PELP1 expression during OGD/R, and this protective effect was blocked upon miR-195-5p downregulation. Collectively, these results indicated that miR-195-5p inhibits testicular IRI-induced pyroptosis by targeting PELP1, suggesting that it has the potential to serve as a novel target for the future development of therapies for testicular torsion.

2023-07-01·Breast cancer research and treatment

Targeting PELP1 oncogenic signaling in TNBC with the small molecule inhibitor SMIP34.

Article

作者: Liu, Junhao ; Vadlamudi, Ratna K ; Sanchez, John R ; Altwegg, Kristin A ; Yang, Xue ; Sareddy, Gangadhara R ; Viswanadhapalli, Suryavathi ; Pratap, Uday P ; Li, Xiaonan ; Panneerdoss, Durga Meenakshi ; Rao, Manjeet K ; Ebrahimi, Behnam ; Liu, Zexuan

PURPOSETriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Oncogenic PELP1 is frequently overexpressed in TNBC, and it has been demonstrated that PELP1 signaling is essential for TNBC progression. The therapeutic utility of targeting PELP1 in TNBC, however, remains unknown. In this study, we investigated the effectiveness of SMIP34, a recently developed PELP1 inhibitor for the treatment of TNBC.METHODSTo ascertain the impact of SMIP34 treatment, we used seven different TNBC models for testing cell viability, colony formation, invasion, apoptosis, and cell cycle analysis. Western blotting and RT-qPCR were used to determine the mechanistic insights of SMIP34 action. Using xenograft and PDX tumors, the ability of SMIP34 in suppressing proliferation was examined both ex vivo and in vivo.RESULTSTNBC cells' viability, colony formation, and invasiveness were all decreased by SMIP34 in in vitro cell-based assays, while apoptosis was increased. SMIP34 treatment promoted the degradation of PELP1 through the proteasome pathway. RT-qPCR analyses confirmed that SMIP34 treatment downregulated PELP1 target genes. Further, SMIP34 treatment substantially downregulated PELP1 mediated extranuclear signaling including ERK, mTOR, S6 and 4EBP1. Mechanistic studies confirmed downregulation of PELP1 mediated ribosomal biogenesis functions including downregulation of cMyc and Rix complex proteins LAS1L, TEX-10, and SENP3. The proliferation of TNBC tumor tissues was decreased in explant experiments by SMIP34. Additionally, SMIP34 treatment markedly decreased tumor progression in both TNBC xenograft and PDX models.CONCLUSIONSTogether, these findings from in vitro, ex vivo, and in vivo models show that SMIP34 may be a useful therapeutic agent for inhibiting PELP1 signaling in TNBC.

项与 PELP1 相关的新闻（医药）

2022-08-29

·生物谷

Cancer Research: 一种针对ER+乳腺癌的ER辅助调节因子一级抑制剂PELP1

乳腺癌是女性最常见的恶性肿瘤，是仅次于肺癌的第二大癌症相关死亡原因，全球每年约有57万人死于乳腺癌(占癌症死亡人数的7%；占所有死亡人数的1%)。乳腺癌是女性最常见的恶性肿瘤，是仅次于肺癌的第二大癌症相关死亡原因，全球每年约有57万人死于乳腺癌(占癌症死亡人数的7%；占所有死亡人数的1%)。大多数BC(70%)雌激素受体α阳性(ER+)。 ER+BC的治疗包括使用抗雌激素(AE)、芳香酶抑制剂(AI)或雌激素受体降解剂(SERD)来调节ER信号。然而，许多患者对这些内分泌治疗产生抵抗力，疾病进展很常见。因此，为患有晚期ER+BC的妇女开发有效的治疗方法是最高的未得到满足的需求。图片来源: https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/35950923/ 近日，来自圣安东尼奥的德克萨斯大学健康科学中心的研究者们在cancer Research杂志上发表了题为“A first-in-class inhibitor of ER coregulator PELP1 targets ER+ breast cancer ”的文章，该研究表明SMIP34是晚期BC中致癌的PELP1信号的一流抑制物。大多数雌激素受体α阳性乳腺癌(ER+BC)患者最初对治疗有反应，但最终随着疾病的进展而产生治疗抵抗。癌基因ER协同调节因子的过度表达，包括脯氨酸、谷氨酸和富含亮氨酸的蛋白1(PELP1)，与BC的进展有关。缺乏抑制PELP1的小分子是一个重大的知识鸿沟。在本研究中，使用酵母双杂交筛选，研究者鉴定了新的PELP1多肽抑制剂(PIPs)。生化分析表明，其中一种多肽PIP1直接与PELP1相互作用，阻断PELP1的致癌功能。对PIP1的计算模型揭示了影响其活性的关键残基，并促进了PELP1小分子抑制剂SMIP34的开发，进一步的分析证实SMIP34直接与PELP1结合。在BC细胞中，SMIP34以PELP1依赖的方式抑制细胞生长。SMIP34不仅抑制野生型(WT)细胞的增殖，还抑制突变型(MT)ER+和耐药(TR)BC细胞的增殖，部分原因是通过蛋白酶体途径诱导PELP1降解。 RNA-seq分析表明，SMIP34处理改变了与雌激素反应、细胞周期和凋亡途径相关的基因的表达。在WT-和MT-ER+BC模型的细胞系来源和患者来源的异种移植中，SMIP34抑制了增殖并显著抑制了肿瘤进展。 SMIP34下调ER信号通路并诱导细胞凋亡图片来源: https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/35950923/ 总之，本研究数据表明PIP1和SMIP34是有效的和特异性的PELP1抑制剂。PIP1和SMIP34均与PELP1直接作用，促进其降解，阻断PELP1下游信号传导，降低WT-、MT-和TR- BC细胞体外、体外和体内的细胞活力。总的来说，本研究结果证明SMIP34是致癌性PELP1信号的一级抑制剂。（生物谷 Bioon.com）参考文献 Kristin A Altwegg et al. A first-in-class inhibitor of ER coregulator PELP1 targets ER+ breast cancer. Cancer Res. 2022 Aug 11;CAN-22-0698. doi: 10.1158/0008-5472.CAN-22-0698.