I am one of the trillions of cells in human body. In our family of cells, I’m a naughty member. I hate walking the planned-out path. I love wandering around. Humans give cells like me a terrifying name: cancer cell. In their world, they never stop fighting against me. They see me as the threat to their lives. Recently I heard human found the natural enemy to my “assistant” PHGDH, a PHGDH inhibitor, and tried to starve me to death. So I fell into a deep worry about my future.
Are you curious about my “assistant” PHGDH? He is my “nutritious partner”. Ok, now let me introduce PHGDH to you.
PHGDH is a gene with the full name of phosphoglycerate dehydrogenase, and it encodes the enzyme 3-phosphoglycerate dehydrogenase. PHGDH is 94% similar to the PHGDH gene in mouse liver. The cDNA of PHGDH is composed of 2,478 bases, which are translated into 533 open reading frames of amino acids. Human have found in their normal tissues that my “assistant” has two different mRNA transcripts: one is 2.1kb, and the other is 710bp. Oops, I forgot to tell you where my assistant’s home is. He lives in the 1q12 area of human chromosome 1. You can see the specific location from the graph below.
The most important role of PHGDH is to encode 3-phosphoglycerate dehydrogenase. This enzyme is the first branching enzyme in the glycolysis-biosynthesis pathway of serine. PHGDH oxidizes the glycolysis intermediate 3–phosphoglycerate into phosphohydroxypyruvic acid, which is eventually turned into serine through a series of enzymatic steps. Serine plays an essential role in the synthesis of other biological molecules needed for protein and cellular growth (e.g. nucleotide, phosphatidylserine, and sphingosine). To tell you a secret: serine is also indispensable for my nutrient supply. With the diagram below you will have a better understanding of how important PHGDH is in the synthesis of serine.
Compared to that in the normal tissue, the expression level of PHGDH is significantly higher in several of other members: breast cancer, melanoma, nasopharyngeal carcinoma, glioma, hepatocellular carcinoma, and small intestinal carcinoma. PHGDH rapidly offers me substantial nutrient for growth, so that Human never stop studying me. In 2011, two research teams in the United States discovered the importance of PHGDH . They found that the elevated PHGDH level caused an increase in the metabolic flux through serine synthesis pathway, which in turn significantly contributed to the influx of glutamate through the tricarboxylic acid cycle-α-ketoglutarate pathway. When they suppressed the gene expression of PHGDH in breast cancer cells, they found suppression of cellular growth and reduction of serine synthesis. Recent reports on serine metabolism from Nature Chemical Biology, March 24 and May 18, 2016, revealed that new type of PHGDH inhibitor could selectively stop the growth of PHGDH-dependent cancer cells. In their recent discovery , Pacold and colleagues used two PHGDH inhibitors: NCT-502 and NCT-503, and they found PHGDH inhibitors showed efficient anti-cancer effects on PHGDH-dependent cancer cells, but not on the non-PHGDH-dependent ones. Besides inhibiting the synthesis of serine, PHGDH inhibitors did not disrupt other amino acids except aspartic acid. In addition, the researchers tested the role of PHGDH inhibitors in the synthesis of serine and found that these inhibitors not only affected the glucose-derived serine synthesis pathway but also reduced the incorporation of endogenous and exogenous serine into nucleotides of one-carbon units. In short, PHGDH inhibitors cut off my nutritious supply, and I can do nothing but starve to death.
Cusabio, as a good partner of life science research, manufactures and provides PHGDH-related products including recombinant proteins in different expression systems and polyclonal antibody. The following shows our product list and pre-validated data images.
His-tag: CSB-YP017920HU >> Yeast
CSB-EP017920HU >> E. Coli
CSB-BP017920HU >> Baculovirus
CSB-MP017920HU >> Mammalian cell
Polyclonal antibody: CSB-PA03255A0Rb
More details about related product, please visit http://www.cusabio.com/
1. Possemato R, Marks KM, Shaul YD, etc. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011 Aug 18;476(7360):346-50.
2. Pacold ME, Brimacombe KR, Chan SH, etc. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016 Jun;12(6):452-8.