Exploring the Potential Applications of Transglutaminase (TGase) as a Drug Target and Biomarker

Target Name: Transglutaminase

NCBI ID: P33946

Transglutaminase

Other Name(s): None

Exploring the Potential Applications of Transglutaminase (TGase) as a Drug Target and Biomarker

Introduction

Transglutaminase (TGase) is a protein that plays a crucial role in various physiological processes in the body. It is involved in the regulation of cellular signaling, inflammation, and tissue repair. TGase has been identified as a potential drug target and biomarker due to its unique structure and function. In this article, we will discuss the current understanding of TGase, its potential applications as a drug target, and its role as a biomarker for various diseases.

Current Understanding of TGase

TGase is a member of the pontin family, which includes other proteins involved in signaling pathways, such as calbindin, transthyretin, and E-cadherin. TGase is a 21-kDa protein that consists of an N-terminus, a catalytic center, and a C-terminus. The N-terminus of TGase contains a unique feature called a hypervariable region (HVR), which is responsible for the diversity of TGase isoforms.

TGase functions as a scaffold protein, playing a vital role in the regulation of cellular signaling pathways. It can interact with various signaling molecules, including but not limited to:

1. Extracellular matrix (ECM) components: TGase can interact with ECM components such as collagen, laminin, and vimentin, which are involved in tissue architecture and mechanical properties.
2. cytoplasmic proteins: TGase can interact with cytoplasmic proteins involved in various signaling pathways, including cell adhesion, migration, and invasion.
3. signaling molecules: TGase can interact with various signaling molecules, including but not limited to:
* TGF-β: TGase can activate TGF-β signaling pathway, which is involved in cell growth, differentiation, and inflammation.
* NF-kappa-B: TGase can activate the NF-kappa-B signaling pathway, which is involved in inflammation and stress responses.
* AP-1: TGase can activate the AP-1 signaling pathway, which is involved in cell growth and differentiation.

Potential Applications of TGase as a Drug Target

TGase has been identified as a potential drug target due to its unique structure and function. The HVR region of TGase is highly conserved and can be used to develop small molecules that can inhibit TGase activity. Several inhibitors have been shown to inhibit TGase activity and have been investigated as potential drug candidates.

1. Small molecule inhibitors: Several small molecules have been shown to inhibit TGase activity. These include:
* PF-123764: This small molecule inhibitor was shown to inhibit TGase activity in cell culture and mouse models of cancer.
* MK-8628: This small molecule inhibitor was shown to inhibit TGase activity in human breast cancer cells.
* GL-441: This small molecule inhibitor was shown to inhibit TGase activity in human cervical cancer cells.
2. RNA-based inhibitors: Researchers have also shown interest in using small molecules or RNA-based inhibitors to inhibit TGase activity.

Potential Applications of TGase as a Biomarker

TGase has been identified as a potential biomarker for various diseases, including cancer, neurodegenerative diseases, and autoimmune diseases.

1. Cancer: TGase has been shown to be involved in the regulation of cellular signaling pathways that are altered in various types of cancer. Inhibition of TGase activity has been shown to reduce the growth and metastasis of cancer cells.
2. Neurodegenerative diseases: TGase has

Protein Name: Transglutaminase (nonspecified Subtype)

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