Last update 01 Nov 2024

PLD1

Last update 01 Nov 2024

Basic Info

Synonyms

choline phosphatase 1, hPLD1, Phosphatidylcholine-hydrolyzing phospholipase D1

+ [4]

Introduction

Function as phospholipase selective for phosphatidylcholine (PubMed:8530346, PubMed:9582313). Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity).

Drugs associated with PLD1

ML299

Target

PLD1 x PLD2

Mechanism

PLD1 inhibitors [+1]

Active Org.

Vanderbilt University Medical Center

Originator Org.

Vanderbilt University Medical Center

Active Indication

Glioblastoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CAY-10593

Target

PLD1

Mechanism

PLD1 inhibitors

Active Org.

Vanderbilt University School of Medicine

Originator Org.

Vanderbilt University School of Medicine

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

PLD1 inhibitors(Yonsei University)

Target

PLD1

Mechanism

PLD1 inhibitors

Active Org.

Yonsei University

Originator Org.

Yonsei University

Active Indication

Lung Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PLD1

100 Translational Medicine associated with PLD1

0 Patents (Medical) associated with PLD1

873

Literatures (Medical) associated with PLD1

01 Dec 2024·Computational and Structural Biotechnology Journal

Molecular interactions between a diphenyl scaffold and PED/PEA15: Implications for type II diabetes therapeutics targeting PED/PEA15 – Phospholipase D1 interaction

Article

Author: Alberga, Domenico ; Saviano, Michele ; Fattorusso, Roberto ; Del Gatto, Annarita ; Zaccaro, Laura ; Malgieri, Gaetano ; Mercurio, Ivan ; Pirone, Luciano ; Pedone, Emilia Maria ; Mangiatordi, Giuseppe Felice ; Della Valle, Maria ; Isernia, Carla ; D'Abrosca, Gianluca ; Russo, Luigi ; Di Gaetano, Sonia

In a recent study, we have identified BPH03 as a promising scaffold for the development of compounds aimed at modulating the interaction between PED/PEA15 (Phosphoprotein Enriched in Diabetes/Phosphoprotein Enriched in Astrocytes 15) and PLD1 (phospholipase D1), with potential applications in type II diabetes therapy. PED/PEA15 is known to be overexpressed in certain forms of diabetes, where it binds to PLD1, thereby reducing insulin-stimulated glucose transport. The inhibition of this interaction reestablishes basal glucose transport, indicating PED as a potential target of ligands capable to recover glucose tolerance and insulin sensitivity. In this study, we employ computational methods to provide a detailed description of BPH03 interaction with PED, evidencing the presence of a hidden druggable pocket within its PLD1 binding surface. We also elucidate the conformational changes that occur during PED interaction with BPH03. Moreover, we report new NMR data supporting the in-silico findings and indicating that BPH03 disrupts the PED/PLD1 interface displacing PLD1 from its interaction with PED. Our study represents a significant advancement toward the development of potential therapeutics for the treatment of type II diabetes.

01 Oct 2024·Journal of Genetics and Genomics

A positive feedback loop between PLD1 and NF-κB signaling promotes tumorigenesis of nasopharyngeal carcinoma

Article

Author: Zhou, Ya-Qing ; Cheng, Xi-Xi ; Liu, Shu-Qiang ; He, Shuai ; Li, Yi-Qi ; Bei, Jin-Xin ; Wei, Pan-Pan ; Luo, Chun-Ling

Phospholipase D (PLD) lipid-signaling enzyme superfamily has been widely implicated in various human malignancies, but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma (NPC). Here, we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis. Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines, correlating with worse disease-free and overall survival in NPC patients. Functional assays further elucidate the oncogenic role of PLD1, demonstrating its pivotal promotion of critical tumorigenic processes such as cell proliferation and migration in vitro, as well as tumor growth in vivo. Notably, our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression. Specifically, PLD1 enhances NF-κB activity by facilitating the phosphorylation and nuclear translocation of RELA, which in turn binds to the promoter of PLD1, augmenting its expression. Moreover, RELA overexpression markedly rescues the inhibitory effects in PLD1-depleted NPC cells. Importantly, the application of the PLD1 inhibitor, VU0155069, substantially inhibits NPC tumorigenesis in a patient-derived xenograft model. Together, our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.

01 Oct 2024·Molecules and Cells

Effects of phospholipase D1 inhibitory peptide on the growth and metastasis of gastric cancer cells

Article

Author: Park, Shin-Young ; Lee, Junwon ; Yoon, Mee-Sup ; Kim, Dongju ; Han, Joong-Soo

Phospholipase D1 (PLD1) contributes to cancer development and progression through its effects on cell proliferation, survival, invasion, metastasis, angiogenesis, drug resistance, and modulation of the tumor microenvironment. Its central role in these processes makes it a promising target for novel cancer treatments aimed at inhibiting its activity and disrupting the signaling pathways it regulates. In this study, we aimed to investigate the effect of PLD1 inhibition on gastric cancer cell growth using a novel peptide inhibitor, TAT-TVTSP. PLD1, which plays a role in cancer progression, catalyzes the conversion of phosphatidylcholine into choline and phosphatidic acid through hydrolysis. To effectively target PLD1 in cells, we engineered TAT-TVTSP by fusing a PLD1-inhibitory peptide (TVTSP) with a cell-penetrating peptide (TAT). We observed that TAT-TVTSP effectively inhibited PLD1 activity in AGS gastric cancer cells. Moreover, TAT-TVTSP significantly inhibited the mammalian target of the rapamycin signaling pathway, including the phosphorylation of key downstream targets such as S6K1, AKT, S473, glycogen synthase kinase-3b, and forkhead box O1. TAT-TVTSP did not induce cell death, but it triggered cell cycle arrest by activating p21 and p27 via AKT phosphorylation. Functional assays revealed that TAT-TVTSP significantly impaired the colony-forming ability of AGS cells, thus inhibiting cell proliferation. Transwell and wound-healing assays revealed that this peptide disrupted the cellular behaviors critical to cancer progression, such as migration and invasion. In vivo, TAT-TVTSP significantly reduced tumor growth in the xenograft model of gastric cancer without any toxicity. Overall, our results suggest that TAT-TVTSP is a novel therapeutic agent for PLD1-mediated cancers.

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PLD1

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