Scientists at the University of Georgia have identified a rare type of glycosylation (more on what that is in a second) which plays a major role in the function of a protein affecting cancer progression.
In other words – another breakthrough in understanding cancer, its causes/source of strength, and – hopefully but promisingly – a cure!
So let’s delve into this study, which is loaded with science.
So, what is this “glycosylation” exactly? Glycosylation is the process where sugar molecules (glucose) in the body’s blood attach to protein molecules, diminishing their effectiveness.
Glycosylation is a bad thing.
The University of Georgia research team of Robert Haltiwanger, Ph.D., has studied specific O-linked modifications (which are the attachment of glucose or fucose to certain atoms in the body) – including one called Notch. Notch is a signaling receptor critical for cell development and is dysregulated in cancers such as breast cancer, multiple myeloma, chronic lymphocytic leukemia – and much more.
“The fact that we found these sugars on Notch was intriguing because Notch is a very important molecule,” Dr. Haltiwanger said. “So, we’ve been curious about how these sugars affect [Notch’s] stability and activity.”
The enzymes responsible for modifying Notch with glucose and fucose are called POFUT1 and POGLUT1 – and the research team were particularly curious as to why. They concluded (and you can read all about it here) in their study that:
“Notch is not functional if you don’t add those sugars. There’s been a lot of work over the years on: Why is that? What is [the sugar] doing?”
They further concluded that fucose and glucose modifications serve as quality-control mechanisms for Notch’s process. When POFUT1 or POGLUT1 (the enzymes involved with these modifications) are knocked out in cell cultures using CRISPR/Cas technology, cells displayed much less Notch on the surface. When they knocked out both enzymes, Notch was almost completely absent.
“It’s like a stamp of approval,” stated Dr. Haltiwanger.” Leave it alone. If you don’t add the sugar, [the Notch proteins] get stuck inside the endoplasmic reticulum, get degraded, and don’t get secreted.”
So, what does all this science talk mean? Well, with this evidence that these sugar compounds are a critical component of Notch activity renders POFUT1 and POGLUT1, real targets for cancer therapy.
