DEFINITION
CD133 is a cellular surface glycoprotein containing five transmembrane regions and two glycosylated extracellular loops with a molecular weight of 97-120 kDa.
Is an important cell surface marker for both stem cells and cancer stem cells in various tissues.
It is Sign of local conditions to be defined.
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
Protein Aminoacids Percentage
As many Stem Cells have GABA receptors
Papers GABA receptors CD133
High levels of GABA can correspond to low levels of glutamate (excitotoxic) and glutamine (proliferation) and therefore should stabilize Stem Cells.
SYNTHESIS AND TURNOVER
mRNA synthesis
protein synthesis
post-translational modifications
????
degradation
Cellular function
-Evidence for CD133 as a stem cell marker
- CD133 surface expression is associated with
stem cells in multiple tissues:
Blood – transplant studies1,2
Brain
Prostrate
Colon
Skin
Liver
Biological Funcion
- cell surface signaling – protrusions?
- stem cell differentiation.
- malignancy.
REGULATION
CD133 SYNTHESIS AND REGULATION
Northern analysis suggests that the mRNA transcript of CD133 is present in a variety of tissues such as the kidney, pancreas, placenta, and fetal liver.
Recent studies demonstrate that CD133 expression is regulated by DNA methylation. In this study, we explored the role of transforming growth factor beta (TGFbeta), a multifunctional cytokine that plays a critical role in chronic liver injury, in the regulation of CD133 expression.
CD133 expression is directly regulated by epigenetic modifications. Therefore, it is possible that CD133 expression by gene demethylation is related to colorectal carcinogenesis.
Recently, it has been reported that colorectal carcinoma is created and propagated by a small number of undifferentiated tumorigenic CD133 cells. Furthermore, it has been reported that CD133 expression is directly regulated by epigenetic modifications. Therefore, it is possible that CD133 expression by gene demethylation is related to colorectal carcinogenesis.
Demethylation of the CD133 gene was detected in 19 out of the 48 (40%) primary colon carcinomas, suggesting that the demethylation of CD133 is frequently observed in colorectal carcinomas.
In this regard, we found that CD133 transcription is controlled by both histone modifications and promoter methylation.
DIAGNOSTIC USE
CD133 AS A STEM CELL MARKER
Due to its expression by haematopoietic progenitors, interest has been directed towards the potential of CD133 as a cell surface marker of adult stem cells.
A role for CD133/AC133 as a marker of stem cells with the capacity to engraft and differentiate to form functional non-haematopoietic adult lineages and contribute to disease amelioration via tissue regeneration is emerging, and thus CD133/AC133 cell therapy may
represent a promising treatment for many diseases.
Tumours are most likely initiated in normal stem cells or their immediate descendants and then perpetuated by a minority of the cells, known as the cancer stem cells (CSCs) or tumour-initiating cells (TICs). Expanding evidence highlights the role of CD133 as a marker of CSCs in various human tumours.
Cells expressing CD133, often in combination with
other markers, represent cancer stem cells in a variety of human
tumours
*Antigenic
phenotype Tumour origin*
CD133, CD44, α1β2 Human prostate tumours
CD133, ABCG2 Human pancreatic adenocarcinoma
CD133 Human colon carcinoma
CD133 Human hepatocellular carcinoma
CD133, nestin Human neural tumours
CD133 Human renal tumours
For more informations
THERAPEUTIC ROLE OF CD 133
Due to the highly restricted expression of CD133 family molecules on plasma membrane protrusions of epithelial and other cell types, in association with membrane cholesterol, a role in the organization of plasma membrane topology has also recently been assigned to this family. Studies have now confirmed the utility of CD133 as a marker of haematopoietic stem cells for human allogeneic transplantation. In addition, CD133 represents a marker of tumour-initiating cells in a number of human cancers, and therefore it may be possible to develop future therapies towards targeting cancer stem cells via this marker.
GENOMIC CONTEXT
chromosome: 4; Location: 4p15.32See
LINKS
http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&dopt=full_report&list_uids=8842
http://www.ncbi.nlm.nih.gov/pubmed/18497886
CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. 2008
http://www.ncbi.nlm.nih.gov/pubmed/20551139
Chiapello Mattia, Coscio Andrea, Sordella Luigi
