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What Is Cathepsin D?

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  • Written By: S. Berger
  • Edited By: Shereen Skola
  • Last Modified Date: 02 December 2016
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The protein known as cathepsin D is found only within cells, and plays a role both in immunity and human disease. Immune cells called macrophages create cathepsin D. Macrophages ingest bacteria, and then undergo apoptosis, or programmed cell death, to ensure that the invading organism is destroyed. The path to apoptosis is caused by activation of cathepsin D within the macrophage.

Cathepsin D's role in apoptosis may be related to another function of digestion. Cells contain compartments called lysosomes, which can hold molecules targeted for destruction. In the lysosome, this protein seems to perform such a function after it has been activated. The activation sequence, the removal of two amino acid groups, along with its function, has led researchers to group this protein with a family of proteins known as peptidases.

The task of peptidases is to break peptide bonds found in proteins. The reason cathepsin D is initially produced as a proenzyme requiring activation is to protect the cell. Were this protein to be produced in an active form, it would attack the proteins inside the cell's own cytoplasm. For this reason, it is first sequestered in the lysosome before activation and digestion.

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When this enzyme is first produced through RNA transcription and translation, it contains a "tag" consisting of a sugar. This tag allows the lysosome membrane proteins to recognize cathepsin D, and to allow it into this carefully protected portion of the cell. This enzyme requires an acidic environment to operate properly, although this safeguard carries its drawbacks. In some disease states, the lysosome may become too acidic, and the enzyme may begin to attack proteins within its membrane.

The gene that codes for this protein, specifically called the CTSD gene, is subject to mutation, as all genes are. Some mutations of the CTSD gene have been associated with diseases such as breast cancer. This is likely due to the gene's role in initiating apoptosis, according to research. Cathepsin D's presence and expression can be used as a tumor marker in breast cancer. Such a role allows researchers to determine the presence of cancerous cells based on the amount of this protein.

The function of cathepsin D may factor into an involvement in Alzheimer's. Another protein in the peptidase family, memapsin, has been linked to tissue destruction in Alzheimer's. Some scientists believe that they have also found a link between a mutation of the CTSD gene and this neurodegenerative disorder, as well.

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serenesurface
Post 3

We're going to do a cathepsin D assay next week in lab. My instructor said that each group is going to get a fluorescent analysis kit with synthetic cathepsin D. Each cathepsin protein will give off a fluorescent light and we'll be able to figure out how much cathepsin D there is.

I think this method is used in quite a few medical procedures, so I'm really excited about this. I think it's going to be very interesting.

ysmina
Post 2

@burcinc-- Yes, I'm also familiar with the study and you are right that cathepsin D is a marker of tumor and it is generally believed that higher levels of it in cells lead to cell death. In case of a tumor, the tumor can spread more easily if there are more cathepsin D.

The study you mentioned was the first of it's kind though. There have been more studies done on this since then. Cathepsin D inhibitors have been used in studies to try and delay cell death in diseased patients. In fact, there are also studies where individuals have been treated with cathepsin D inhibitors before disease to learn about it's capacity to prevent or delay disease.

Studies are still continuing on this but I think we're going to be able to use this knowledge in a meaningful way in cancer treatments sooner or later.

burcinc
Post 1

I've heard about the link between cathepsin D and cancer the article mentioned as well.

I remember it well because the research on this was taking place in the late 90s, around the time my aunt was diagnosed with breast cancer. When this was happening, I was thinking that doctors would be able to find a way to limit cathepsin D in the cells and could prevent the spread of the tumor that way.

As far as I remember, the only conclusion that was reached with this study is that higher Cathepsin D levels is associated with more deadly tumors. I don't think we have been able to go a step further and use this process in a way that could fight cancer right?

Does anyone else remember this study?

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