NANOG

What is NANOG?

Nanog is a homeobox transcription factor discovered in 2003. It is considered to play a key role in the maintenance of totipotency of ES cells and is a key factor in self-renewal of ES cells. It plays a very important role in maintaining the multi-function of early embryos of embryonic stem cells and preventing them from differentiating into endoderm.

The Structure of NANOG

The human Nanog gene, Nanog1 (Gene ID: 13376297), is located on chromosome 12 and consists of 4 exons and 3 introns. It has an open reading frame ((ORF)) of 915 bp.

In humans, the Nanog protein encoded by the Nanog1 gene contains 305 amino acids and has a highly conserved DNA homologous binding region. The structure of the protein can be roughly divided into three regions: the N-terminal "interference" domain (ND), DNA homologous domain (H) and the C-terminal transcriptional activation domain.

There are 95 residues rich in serine and threonine in the N-terminal "interference" domain.

The DNA homologous domain contains 60 amino acid residues, which can bind to DNA and interact with protein.

The C-terminal region contains 150 amino acid residues and contains two subdomains: CD1 and CD2. They are responsible for trans-activation. In addition, there is a tryptophan-rich domain (WRD) between the two subdomains, which is involved in dimerization.

These two subdomains are responsible for trans-activation. In addition, there is a tryptophan-rich domain (WRD) between the two subdomains involved in dimerization.

The Expression of NANOG

Nanog was mainly expressed in the inner cell mass (inner cell mass, ICM) of blastocyst. The expression of Nanog gene is closely related to cell division, differentiation. Nanog can maintain the self-renewal and pluripotency of embryonic stem cells.

The expression was higher in undifferentiated embryonic stem cells and lower in differentiated embryonic stem cells.

The expression of Nanog gene decreased gradually with the deepening of cell differentiation, until it was not expressed in fully differentiated cells.

The Function of NANOG

Nanog not only maintains the self-renewal and pluripotency of embryonic stem cells, but also regulates the cell cycle of ESC. NANOG can affect many cell cycle regulators, among which cyclin D1 has been proved to be directly regulated by NANOG. In addition, Nanog plays an important role in tumorigenesis and development. The expression of Nanog gene is closely related to tumor differentiation, and plays an important role in promoting the occurrence and development of tumor cells and anti-apoptosis. It can be used as a marker of cell totipotency and tumor diagnosis.

Overexpression of NANOG in tumor cells affects some important cancer phenotypes, including cell proliferation, cell migration and invasion, drug resistance and hypoxic stress.

NANOG can be activated by a variety of stimulating factors in malignant tumors. In hypoxic environment, NANOG can be activated by HIF-1 α or HIF-2 α signaling pathway. In addition, NANOG can regulate drug resistance by up-regulating MDR-1, IGF2BP3 and YAP1.

The Latest Research Progress

Recent studies have found a clinical correlation between NANOG and the early stages of oral squamous cell carcinoma (OSCC) tumor development. Nanog expression is an early predictor of oral cancer risk in patients with pharyngeal muscular dystrophy.

Meta-analysis to determine whether the expression of Nanog was associated with the prognosis or clinicopathological features of (NSCLC) in non-small cell lung cancer showed that the high expression of Nanog was significantly correlated with overall survival (OS), tumor differentiation and TNM stage.

However, there was no significant relationship between the expression of Nanog and the clinicopathological features such as sex, age, tumor size and lymph node metastasis. In patients with NSCLC, the high expression of Nanog is associated with poor prognosis, and Nanog can be used as a prognostic factor for NSCLC.

Drug resistance and disease recurrence are the main reasons for the invasiveness of ovarian cancer. Nanog is a key transcription factor of pluripotency, which is involved in tumorigenesis and chemotherapy resistance of OC. Targeting Nanog may be used as a research direction in the treatment of OC.

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