MicroProtein and Stress - Seeker's Thoughts

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MicroProtein and Stress

Biology study is improving, researchers have uncovered detail into microprotein. 
They discovered that a microprotein called PIGBOS found in the powerhouse of the cells – mitochondria- contributes to mitigating stress happening within the cells.
This is an advance that may lead to a better understanding of disease conditions like cancer.

The work published on October 25, 2019, in the journal Nature Communications, indicates that PIGBOS could be a target for human disease.

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According to the Salk professor Alan saghatelian, co-corresponding author of the study. PIGBOS was made of 54 amino acid molecules and indicated that the microprotein could be a target for cell stress-based human disease like and neurodegeneration.

What is microprotein?

Micro Proteins (MiPs) are short, usually single domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect. 

In animals and plants, microprotein has been found to greatly influence the biological process. Because of microprotein dominant effects on their targets microprotein is currently being studied for potential in biotechnology.

In structure, microprotein is generally small proteins with a single protein domain. The active form of micro proteins is translated from smORF. 

The smORF codons in which microproteins are translated from can be less than 100 codons. However, not all microprotein is small, and the name was given because their actions are analogous to miRNAs.
More about the Research

To track and find the function of proteins, researchers attach a jelly fish-derived probe called the green fluorescent protein (GFP) to them, which glows and indicated the protein’s presence in cells.

However, the researchers of the current study ran into a roadblock when they try to mark PIGBOS with GFP as the microprotein was too small relative to the size of the fluorescent tag. 

They solved the problem using a less common approach called split GFP where they fused just a small part of GFP, called a beta-strand, to PIGBOS.  

With the new set up, the researchers could see PIGBOS, and the study of it interacted with other proteins.

Study co-author Qian Chu from Salk institute said – as they mapped the micro protein’s location, they found that it sat on the outer membrane of the mitochondria and made contact with protein on other organelle called endoplasmic reticulum (ER). PIGBOS is like a connection to link mitochondria and ER together.

PIGBOS communicated with CLCC1 to regulate stress in the ER.  "Researchers hadn't seen that before in microprotein--and it's rare in just normal proteins. The study noted that without PIGBOS, the ER is more likely to experience stress and form misshapen proteins.

This may lead to the cell trying to clear out the irregular proteins, failing which it may initiate a self-destruct sequence and die. According to the Chu and his team, it was unusual to see a mitochondrial protein playing a role in the unfolded protein response.  The new understanding of PIGBOS could open the door for future therapies targeting cell stress. "Going forward, we might consider how PIGBOS is involved in a disease like cancer,

ER is more stressed in cancer patients than in a normal person and added that ER stress regulation could be a good target to tackle the disease. 

Current cancer treatment options

Many cancer treatments are available. Your treatment options will depend on several factors, such as the type and stage of your cancer, your general health, and your preferences. Together you and your doctor can weigh the benefits and risks of each cancer treatment to determine which is best for you.

Cancer treatment options include:

·         Surgery. The goal of surgery is to remove cancer or as much cancer as possible.

·         Chemotherapy. Chemotherapy uses drugs to kill cancer cells.

·         Radiation therapy. Radiation therapy uses high-powered energy beams, such as X-rays or protons, to kill cancer cells. Radiation treatment can come from a machine outside your body (external beam radiation), or it can be placed inside your body (brachytherapy).

·         Bone marrow transplant. Your bone marrow is the material inside your bones that makes blood cells from blood stem cells. A bone marrow transplant, also known as a stem cell transplant, can use your own bone marrow stem cells or those from a donor.

A bone marrow transplant allows your doctor to use higher doses of chemotherapy to treat your cancer. It may also be used to replace diseased bone marrow.

·         Immunotherapy. Immunotherapy, also known as biological therapy, uses your body's immune system to fight cancer. Cancer can survive unchecked in your body because your immune system doesn't recognize it as an intruder. Immunotherapy can help your immune system "see" cancer and attack it.

·         Hormone therapy. Some types of cancer are fuelled by your body's hormones. Examples include breast cancer and prostate cancer. Removing those hormones from the body or blocking their effects may cause the cancer cells to stop growing.

·         Targeted drug therapy. Targeted drug treatment focuses on specific abnormalities within cancer cells that allow them to survive.

·         Cryoablation. This treatment kills cancer cells with cold. During cryoablation, a thin, wand-like needle (cryoprobe) is inserted through your skin and directly into the cancerous tumor. Gas is pumped into the cryoprobe in order to freeze the tissue. Then the tissue is allowed to thaw. The freezing and thawing process is repeated several times during the same treatment session in order to kill the cancer cells.

·         Radiofrequency ablation. This treatment uses electrical energy to heat cancer cells, causing them to die. During radiofrequency ablation, a doctor guides a thin needle through the skin or through an incision and into the cancer tissue. High-frequency energy passes through the needle and causes the surrounding tissue to heat up, killing the nearby cells.

·         Clinical trials. Clinical trials are studies to investigate new ways of treating cancer. Thousands of cancer clinical trials are underway.


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