TUSC3 Membrane Protein Introduction

Introduction of TUSC3

Tumor suppressor candidate 3 (TUSC3) is a putative tumor suppressor located at chromosomal region 8p22. It is often lost in epithelial cancers, such as prostate, breast, oral squamous, pancreatic, colorectal or ovarian cancer. TUSC3 is localized to the endoplasmic reticulum in an oligosaccharyl tranferase complex responsible for the N-glycosylation of proteins. Together with magnesium transporter 1 (MAGT1) and non-imprinted in Prader-Willi/Angelman syndrome region protein 2 (NIPA2), TUSC3 is deeply involved in vertebrate plasma membrane transport of Mg²⁺. It has been found to modulate intracellular Mg²⁺ concentrations in a human cell line and is pivotal for many biochemical functions and morphological and cytological changes. Epigenetic silencing of TUSC3 has been associated with poor prognosis.

Function of TUSC3 Membrane Protein

TUSC3 has also been identified as a potential tumor suppressor gene. Defects in TUSC3 caused by deletions or mutations are frequently associated with mental retardation. In prostate, breast, oral squamous, pancreatic, colorectal or ovarian cancer, TUSC3 is significantly down-regulated in tumor tissues. Homozygous deletion of TUSC3 and epigenetic regulation of TUSC3 expression through promoter methylation are considered to be potential aetiological factors related to tumor dissemination and progression. According to the Oncomine database, the expression of TUSC3 gene is significantly downregulated in patients with ovarian cancer, indicating a potential clinical relevance of TUSC3 in the pathogenesis of ovarian cancer. Moreover, epigenetic silencing of TUSC3 has been associated with poor prognosis of ovarian cancer, and hypermethylation of its promoter provides an independent biomarker of overall and disease-free survival in ovarian cancer patients.

Fig.1 Model for TUSC3 functions in CRC. (Burgermeister, 2017)

Application of TUSC3 Membrane Protein in Literature

1. Kratochvílová K., et al. Tumor suppressor candidate 3 (TUSC3) prevents the epithelial-to-mesenchymal transition and inhibits tumor growth by modulating the endoplasmic reticulum stress response in ovarian cancer cells. Int J Cancer. 2015, 137(6): 1330-40. PubMed ID: 25735931
   
   

   The article confirms the tumor-suppressive function of TUSC3 and identifies the possible mechanism driving TUSC3-deficient ovarian cancer cells toward a malignant phenotype.

2. Fan X., et al. Decreased TUSC3 promotes pancreatic cancer proliferation, invasion and metastasis. PLoS One. 2016, 11(2): e0149028. PubMed ID: 26871953
   
   

   The article reports that the reduction of immunological TUSC3 staining is a prognostic factor for the low survival rate of patients with pancreatic cancer. The decreased of TUSC3 can promote pancreatic cancer cell proliferation, invasion, and metastasis.

3. Gu Y., et al. TUSC3 promotes colorectal cancer progression and epithelial-mesenchymal transition (EMT) through WNT/β-catenin and MAPK signalling. J Pathol. 2016, 239(1): 60-71. PubMed ID: 27071482
   
   

   The results of this article show that TUSC3 may be responsible for alternations in the proliferation ability, aggressiveness, and invasive/metastatic potential of colorectal cancer.

4. Jiang Z., et al. TUSC3 suppresses glioblastoma development by inhibiting Akt signaling. Tumour Biol. 2016, 37(9): 12039-12047. PubMed ID: 27177902
   
   

   The article reveals that TUSC3 regulates proliferation and invasion of glioblastoma multiform cells by inhibiting the activity of the Akt signaling pathway.

5. Mohorko E., et al. Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation. Structure. 2014, 22(4): 590-601. PubMed ID: 24685145
   
   

   Authors in this group found that N33/Tusc3 increased glycosylation efficiency for a subset of human glycoproteins by slowing glycoprotein folding.

TUSC3 Preparation Options

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Reference

1. Burgermeister E, et al. (2017). Epigenetic silencing of tumor suppressor candidate 3 confers adverse prognosis in early colorectal cancer. Oncotarget. 8(49), 84714-84728.

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