Last update 01 Nov 2024

PRAG1

Last update 01 Nov 2024

Basic Info

Synonyms

DKFZp761P0423, Inactive tyrosine-protein kinase PRAG1, NACK

+ [7]

Introduction

Catalytically inactive protein kinase that acts as a scaffold protein. Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth (By similarity). Promotes Src family kinase (SFK) signaling by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism (By similarity). Acts as a critical coactivator of Notch signaling (By similarity).

Drugs associated with PRAG1

SSTK-214

Target

PRAG1

Mechanism

PRAG1 inhibitors

Active Org.

StemSynergy Therapeutics, Inc.

Originator Org.

StemSynergy Therapeutics, Inc.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PRAG1

100 Translational Medicine associated with PRAG1

0 Patents (Medical) associated with PRAG1

Literatures (Medical) associated with PRAG1

01 Dec 2024·Current Opinion in Structural Biology

View from the PEAKs: Insights from structural studies on the PEAK family of pseudokinases

Review

Author: Lucet, Isabelle S ; Daly, Roger J ; Lucet, Isabelle S. ; Daly, Roger J.

The PEAK family of pseudokinase scaffolds, comprising PEAK1 (originally termed SgK269), PEAK2 (SgK223, the human orthologue of rat Pragmin) and PEAK3 (C19orf35), have emerged as important regulators and integrators of cellular signaling and also play oncogenic roles in a variety of human cancers. These proteins undergo both homo- and heterotypic association that act to diversify signal output. Recently, structural and functional characterization of PEAK3 and its protein-protein interactions have shed light on PEAK signaling dynamics and the interdependency of PEAK family members, how PEAK dimerization regulates the binding of downstream effectors, and how 14-3-3 binding acts to regulate PEAK3 signal output. These important advances form the basis of this review.

01 Jul 2024·The Plant Journal

Genome sequence and cell biological toolbox of the highly regenerative, coenocytic green feather alga Bryopsis

Article

Author: Toyoda, Atsushi ; Edzuka, Tomoya ; Tanaka, Hiroyuki ; Uesaka, Kazuma ; Hanawa, Daiki ; Ogawa, Harumi A ; Ochiai, Kanta K ; Shirae-Kurabayashi, Maki ; Goshima, Gohta ; Itoh, Takehiko

SUMMARYGreen feather algae (Bryopsidales) undergo a unique life cycle in which a single cell repeatedly executes nuclear division without cytokinesis, resulting in the development of a thallus (>100 mm) with characteristic morphology called coenocyte. Bryopsis is a representative coenocytic alga that has exceptionally high regeneration ability: extruded cytoplasm aggregates rapidly in seawater, leading to the formation of protoplasts. However, the genetic basis of the unique cell biology of Bryopsis remains poorly understood. Here, we present a high‐quality assembly and annotation of the nuclear genome of Bryopsis sp. (90.7 Mbp, 27 contigs, N50 = 6.7 Mbp, 14 034 protein‐coding genes). Comparative genomic analyses indicate that the genes encoding BPL‐1/Bryohealin, the aggregation‐promoting lectin, are heavily duplicated in Bryopsis, whereas homologous genes are absent in other ulvophyceans, suggesting the basis of regeneration capability of Bryopsis. Bryopsis sp. possesses >30 kinesins but only a single myosin, which differs from other green algae that have multiple types of myosin genes. Consistent with this biased motor toolkit, we observed that the bidirectional motility of chloroplasts in the cytoplasm was dependent on microtubules but not actin in Bryopsis sp. Most genes required for cytokinesis in plants are present in Bryopsis, including those in the SNARE or kinesin superfamily. Nevertheless, a kinesin crucial for cytokinesis initiation in plants (NACK/Kinesin‐7II) is hardly expressed in the coenocytic part of the thallus, possibly underlying the lack of cytokinesis in this portion. The present genome sequence lays the foundation for experimental biology in coenocytic macroalgae.

01 Nov 2023·Radiotherapy and Oncology

Prostate cancer radiogenomics reveals proliferative gene expression programs associated with distinct MRI-based hypoxia levels

Article

Author: Seierstad, Therese ; Aarnes, Eva-Katrine ; Helgeland, Hanna ; Vlatkovic, Ljiljana ; Skingen, Vilde Eide ; Ragnum, Harald Bull ; Hompland, Tord ; Salberg, Unn Beate ; Hole, Knut Håkon ; Lyng, Heidi ; Fjeldbo, Christina Sæten

BACKGROUND AND PURPOSEThe biology behind individual hypoxia levels in patient tumors is poorly understood. Here, we used radiogenomics to identify associations between magnetic resonance imaging (MRI)-based hypoxia levels and biological processes derived from gene expression data in prostate cancer.MATERIALS AND METHODSFor 85 prostate cancer patients, MRI-based hypoxia images were constructed by combining diffusion-weighted images reflecting oxygen consumption and supply. The ability to differentiate hypoxia levels in these images was verified by comparison with matched biopsy sections stained for the hypoxia marker pimonidazole. For MRI-defined hypoxia levels, corresponding hypoxic fractions were calculated and correlated with biopsy gene expression profiles. Biological processes were predicted by gene set enrichment analysis (GSEA) and validated by immunohistochemistry (Ki67 proliferation marker, reactive stroma grade) and RT-PCR (MYC).RESULTSGenes with correlation between expression level and hypoxic fraction were identified for 56 MRI-based hypoxia levels. At all levels, GSEA identified proliferation as the predominant biological process enriched among the correlating genes. Two independent proliferative gene signatures were developed. The Peak1 signature, upregulated at moderate/severe hypoxia, reflected MYC upregulation and high Ki67-proliferation index of cancer cells in pimonidazole-positive regions. The Peak2 signature, upregulated at mild to non-hypoxic levels, was associated with fibroblast gene signature and reactive stroma grade. High scores of both Peak1 and Peak2 indicated elevated risk of biochemical recurrence in multiple cohorts.CONCLUSIONRadiogenomics identified two gene expression programs activated at different hypoxia levels, reflecting proliferation of cancer cells and stroma cells. Genes involved in these programs could be candidate targets for intervention.

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