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Last update 23 Jan 2025

PGGT1B

Last update 23 Jan 2025

Basic Info

Synonyms

BGGI, Geranylgeranyl transferase type I subunit beta, Geranylgeranyl transferase type-1 subunit beta

+ [5]

Introduction

Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Known substrates include RAC1, RAC2, RAP1A and RAP1B.

Drugs associated with PGGT1B

Gliotoxin

Target

Ftase x PGGT1B

Mechanism

Ftase inhibitors [+1]

Active Org.

Imperial College London

Originator Org.

Imperial College London

Active Indication

Breast Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PGGT1B

100 Translational Medicine associated with PGGT1B

0 Patents (Medical) associated with PGGT1B

101

Literatures (Medical) associated with PGGT1B

01 Nov 2024·Journal of Thoracic Oncology

FGTI-2734 Inhibits ERK Reactivation to Overcome Sotorasib Resistance in KRAS G12C Lung Cancer

Article

Author: Sebti, Said M ; Kazi, Aslamuzzaman ; Bandyopadhyay, Dipankar ; Ghosh, Deblina ; Kantilal Vasiyani, Hitesh Kumar ; Trevino, Jose ; Shah, Rachit D ; Vudatha, Vignesh

KRAS G12C targeted therapies, such as sotorasib, represent a major breakthrough, but overall response rates and progression-free survival for patients with KRAS G12C lung cancer are modest due to the emergence of resistance mechanisms involving adaptive reactivation of ERK, which requires wild-type (WT) HRAS and NRAS membrane localization. Here, we demonstrate that the dual farnesyltransferase (FT) and geranylgeranyltransferase-1 (GGT-1) inhibitor FGTI-2734 inhibits WT RAS membrane localization and sotorasib-induced ERK feedback reactivation, and overcomes sotorasib adaptive resistance. The combination of FGTI-2734 and sotorasib is synergistic at inhibiting the viability and inducing apoptosis of KRAS G12C lung cancer cells, including those highly resistant to sotorasib. FGTI-2734 enhances sotorasib's anti-tumor activity in vivo leading to significant tumor regression of a patient-derived xenograft (PDX) from a patient with KRAS G12C lung cancer as well as several xenografts from highly sotorasib-resistant KRAS G12C human lung cancer cells. Importantly, treatment of mice with FGTI-2734 inhibited sotorasib-induced ERK reactivation in KRAS G12C PDX, and treatment of mice with the combination of FGTI-2734 and sotorasib were also significantly more effective at suppressing in vivo the levels of P-ERK in sotorasib-resistant human KRAS G12C lung cancer xenografts as well as a PDX. Our findings provide a foundation for overcoming sotorasib resistance and potentially improving the treatment outcomes of KRAS G12C lung cancer.

30 Jan 2024·Gene

Revelation of genetic diversity and genomic footprints of adaptation in Indian pig breeds

Article

Author: Chauhan, Anuj ; A, Vani ; Vempadapu, Varshini ; Mehrotra, Arnav ; Ranjan Sahu, Amiya ; Dutt, Triveni ; Mahala, Sudarshan ; Kumar, Amit ; Firdous Ahmad, Sheikh ; Kumar De, Arun ; Chandra Janga, Sarath

In the present study, the genetic diversity measures among four Indian domestic breeds of pig namely Agonda Goan, Ghurrah, Ghungroo, and Nicobari, of different agro-climatic regions of country were explored and compared with European commercial breeds, European wild boar and Chinese domestic breeds. The double digest restriction site-associated DNA sequencing (ddRADseq) data of Indian pigs (102) and Landrace (10 animals) were generated and whole genome sequencing data of exotic pigs (60 animals) from public data repository were used in the study. The principal component analysis (PCA), admixture analysis and phylogenetic analysis revealed that Indian breeds were closer in ancestry to Chinese breeds than European breeds. European breeds exhibited highest genetic diversity measures among all the considered breeds. Among Indian breeds, Agonda Goan and Ghurrah were found to be more genetically diverse than Nicobari and Ghungroo. The selection signature regions in Indian pigs were explored using iHS and XP-EHH, and during iHS analysis, it was observed that genes related to growth, reproduction, health, meat quality, sensory perception and behavior were found to be under selection pressure in Indian pig breeds. Strong selection signatures were recorded in 24.25-25.25 Mb region of SSC18, 123.25-124 Mb region of SSC15 and 118.75-119.5 Mb region of SSC2 in most of the Indian breeds upon pairwise comparison with European commercial breeds using XP-EHH. These regions were harboring some important genes such as EPHA4 for thermotolerance, TAS2R16, FEZF1, CADPS2 and PTPRZ1 for adaptability to scavenging system of rearing, TRIM36 and PGGT1B for disease resistance and CCDC112, PIAS1, FEM1B and ITGA11 for reproduction.

01 Dec 2023·Journal of Periodontology

Prenyltransferase gene expression reveals an essential role of prenylation for the inflammatory response in human gingival fibroblasts

Article

Author: Bachmann, Hagen S. ; Friedmann, Anton ; Diehl, Daniel

AbstractBackgroundPrenyltrasferases (PTases) are a class of enzymes known to be responsible for promoting posttranslational modification at the carboxyl terminus of proteins containing a so‐called CaaX‐motif. The process is responsible for proper membrane localization and the appropriate function of several intracellular signaling proteins. Current research demonstrating the pathomechanistic importance of prenylation in inflammatory illnesses emphasizes the requirement to ascertain the differential expression of PT genes under inflammatory settings, particularly in periodontal disease.MethodsTelomerase‐immortalized human gingival fibroblasts (HGF‐hTert) were cultured and treated with either inhibitors of prenylation (PTI) lonafarnib, tipifarnib, zoledronic acid, or atorvastatin at concentrations of 10 μM in combination with or without 10 μg Porphyromonas gingivalis lipopolysaccharide (LPS) for 24 h. Prenyltransferase genes FNTB, FNTA, PGGT1B, RABGGTA, RABGGTB, and PTAR1 as well as inflammatory marker genes MMP1 and IL1B were detected using quantitative real‐time polymerase chain reaction (RT‐qPCR). Immunoblot and protein immunoassay were used to confirm the results on the protein level.ResultsRT‐qPCR experiments revealed significant upregulation of IL1B, MMP1, FNTA, and PGGT1B upon LPS treatment. PTase inhibitors caused significant downregulation of the inflammatory cytokine expression. Interestingly, FNTB expression was significantly upregulated in response to any PTase inhibitor in combination with LPS, but not upon LPS treatment only, indicating a vital role of protein farnesyltransferase in the proinflammatory signaling cascade.ConclusionsIn this study, distinct PTase gene expression patterns in pro‐inflammatory signaling were discovered. Moreover, PTase inhibiting drugs ameliorated inflammatory mediator expression by a significant margin, indicating that prenylation is a major pre‐requisite for innate immunity in periodontal cells.

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PGGT1B

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