Last update 01 Nov 2024

RABGGTB

Last update 01 Nov 2024

Basic Info

Synonyms

Geranylgeranyl transferase type II subunit beta, Geranylgeranyl transferase type-2 subunit beta, GGTase-II-beta

+ [7]

Introduction

Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and RAB7A.

Drugs associated with RABGGTB

CN118121702

Patent Mining

Target

RABGGTB

Mechanism-

Active Org.

Skin Diseases Hospital, China Academy of Medical Science

Originator Org.

Skin Diseases Hospital, China Academy of Medical Science

Active Indication

Immune System Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with RABGGTB

100 Translational Medicine associated with RABGGTB

0 Patents (Medical) associated with RABGGTB

Literatures (Medical) associated with RABGGTB

01 Jan 2024·Brain Research Bulletin

RABGGTB plays a critical role in ALS pathogenesis

Article

Author: Dong, Hui ; Liu, Yaling ; Yang, Jing ; Liu, Qi ; Xin, Cheng ; Huo, Jia ; Ma, Haiyang ; Li, Rui

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unknown causes, which mainly affects motor neurons in the anterior horn of the spinal cord, brain stem, and cerebral cortex, also known as motor neuron disease. An important pathological feature of ALS is the formation of aggregates of mutant SOD1 protein, CTF25 of TDP-43, or other abnormal proteins in motor neurons, which require autophagy for degradation. Protein prenylation is known to participate in membrane association and proper localization of proteins. RABGGTB is the β subunit of GGTase II (one of the prenyltransferases) that can regulate autophagy via Rab7 geranylgeranylation. In this study, we overexpressed RABGGTB via lentiviral transfection in NSC34-hSOD1G93A and TDP-43 cells. Overexpression of RABGGTB improved ALS cell proliferation by facilitating autophagosome-lysosome fusion. Furthermore, the abnormal aggregation of SOD1 protein was reduced. This indicates that protein prenylation is important for the proliferation and autophagy of cells autophagy. Enhanced autophagy has been observed in two of the most widely used ALS cell models. These findings indicate the widespread applicability of prenylation in ALS. In summary, overexpression of RABGGTB improved the geranylgeranylation of the Rab7 protein and had a positive effect on cells. These findings provide insights into the development of a novel therapeutic strategy for ALS.

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.

12 Apr 2023·International journal of molecular sciences

Prenyl Transferases Regulate Secretory Protein Sorting and Parasite Morphology in Toxoplasma gondii.

Article

Author: Long, Shaojun ; He, Kai ; Aleem, Muhammad-Tahir ; Wang, Qiang-Qiang

Protein prenylation is an important protein modification that is responsible for diverse physiological activities in eukaryotic cells. This modification is generally catalyzed by three types of prenyl transferases, which include farnesyl transferase (FT), geranylgeranyl transferase (GGT-1) and Rab geranylgeranyl transferase (GGT-2). Studies in malaria parasites showed that these parasites contain prenylated proteins, which are proposed to play multiple functions in parasites. However, the prenyl transferases have not been functionally characterized in parasites of subphylum Apicomplexa. Here, we functionally dissected functions of three of the prenyl transferases in the Apicomplexa model organism Toxoplasma gondii (T. gondii) using a plant auxin-inducible degron system. The homologous genes of the beta subunit of FT, GGT-1 and GGT-2 were endogenously tagged with AID at the C-terminus in the TIR1 parental line using a CRISPR-Cas9 approach. Upon depletion of these prenyl transferases, GGT-1 and GGT-2 had a strong defect on parasite replication. Fluorescent assay using diverse protein markers showed that the protein markers ROP5 and GRA7 were diffused in the parasites depleted with GGT-1 and GGT-2, while the mitochondrion was strongly affected in parasites depleted with GGT-1. Importantly, depletion of GGT-2 caused the stronger defect to the sorting of rhoptry protein and the parasite morphology. Furthermore, parasite motility was observed to be affected in parasites depleted with GGT-2. Taken together, this study functionally characterized the prenyl transferases, which contributed to an overall understanding of protein prenylation in T. gondii and potentially in other related parasites.

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RABGGTB

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