Ubiquitination: An Unneeded Protein Analysis

Since we have already known the amino sequence of the protein in previous step, we can narrow down the targeting ubiquitin ligase based on existing research data such as papers, NCBI data.

One wrong amino acid can change the shape of the protein and lead to a malfunctioning protein.

In UNIT 7 you learned about the basics structure as well as the basic functions of deoxyribonucleic acid. You learned that deoxyribonucleic acid carries an “instruction manuel” to produce proteins that are responsible for passing traits from your parents to you. As you demonstrated in the previous activity, deoxyribonucleic acid is made of four nucleotides base pairs: adenine, thymine, cytosine, and guanine. They are often abbreviated as A, T, C, and G. The uniqueness of deoxyribonucleic acid is not particularly in just these 4 subunits, but how they are arranged. In this activity you will recreate protein synthesis.

I found this topic interesting and informative because it defined the multiple ways that a protein could be affected in the body and lead to a disease. While some people find biochemistry as a whole intimidating, I find it fascinating that pathways and complexes can interconnect and link. Interconnections can cause more than one result. This concept helped me understand how a disease, such as Opitz syndrome, is so challenging to cure. Curing the effects of B-box 1 or 2 may or may not lead to realignment of microtubules. There could be downstream effects that take place in other areas. As a result, hard work and a plethora of experimentation is necessary to be able to isolate pathways and cure this troubling disease.

The main point of the article was to find out why the VPS35 gene mutation lead to neurodegeneration. In class, we discussed a little bit about the mitochondria and how it’s the powerhouse of the cell, and how that is what really gives us most of our energy currency, but we never covered anything in this much depth about any organelle. The mitochondria has always been my favorite organelle, so being able to really dive deep into the topic of fission within the mitochondria amazes me. Another mind boggling topic is thinking about how many more processes go on within that one organelle that I don’t know about, yet. What I learned about had to do with the fission process. Just imagine how many other processes go on in the mitochondria alone. This article helped me gain a better appreciation for the course material by bringing me back down to Earth a little bit. It’s extremely easy to get caught up with important, or even non-important issues in our lives. However, when you read a scholarly science article that deals with the subject of biology, it exposes one part of a certain world; you allow yourself to calm down a little bit while truly understanding the importance of biology. I gain more and more respect for science and the subject of biology each time I learn something new. This article allowed me to understand how much we, as humans, take for granted. I know that I don’t always treat my body with the respect it deserves and this article has inspired me to try to make a change in myself and give my body, cells, and organelles the respect they

DVL 1 protein is a cytoplasmic phosphoprotein produced by DVL 1 gene regulating the cell formations and a transducer particle for the developmental processes such as neuroblast specification and segmentation.1 In Wnt Signalling Pathway, the DVL 1 protein works by binding to C-terminus of frizzled receptors and transduce the wnt signal in both canonical and non-canonical pathway.2 These pathways activation lead to the accumulation of beta catenin protein in the cell which known to have important roles in proliferation and formation of the cells.2

Within the 2H88 complex II protein, an inhibitor was also discovery when they were analyzing the structure of it. The malate like intermediate, TEO, mentioned before was found to be an inactive suicide inhibitor. During normal functions, without the presence of TEO, FAD functions normally by grabs the hydrogen from Succinate and form FADH2. However, when TEO is present such inhibitor serves as a negative feedback (Shen, J.T.et. al. 2006). When too much Ubiquinone were produced, and not enough electrons are transferred fast enough to form ubiquinol, the excessive Ubiquinone can oxidize TEO to oxaloacetate (OAA) . OAA then inhibits succinate oxidation. TEO binds to FAD functions to inhibit in the form of Oxaloacetate the flavin protein

These domains are rich in cysteines that for 3 disulfide bridges. Mutations due to cysteine substitution cause a disruption in disulfide bridges. [1] The protein will become misfolded and will be unable to bind calcium. According to a study by Reinhardt, calcium protects fibrillin-1 from proteolytic degradation. [2]

These cyclins are responsible for regulating the cell's transition from G1 to S phase 3. Patients with breast cancer exhibit abnormally high levels of Cyclin E 3,4. The elevated levels of Cyclin E cause malignant cells to proliferate faster with less restriction on cyclin dependent checkpoints in the cell cycle. Researchers are investigating methods similar to ubiquitylation in order to keep cyclin levels in check and prevent cancer cells from spreading 3. "Peptide vaccines" could be used to tag the cyclin's regulatory subunit, much like ubiquitin, labeling it for destruction by proteosomes 3,4. Bringing cyclin levels back down to a low concentration would prevent cancer cells from entering S phase and

The aggregation of misfolded proteins may occur in different cells and regions of the body, originating a variety of disorders. When affecting the central nervous system (CNS) proteinopathies are often neurodegenerative disorders, and can be characterized by one or more proteinaceous aggregates (Bayer, 2015). Neurons are quite sensitive to the effects of misfolded proteins due to their post-mitotic nature and structure (Wolfe, 2012). Indeed, the long and narrow axonal projections of neurons can be easily clogged by accumulating proteins or by inefficient transport of nutrients and organelles (Wolfe, 2012). Additionally, accumulated misfolded proteins cannot be diluted through cell division, thereby turning neuron’s integrity highly dependent

It is action is mediated by Protein Kinase G (PKG) , a cGMP-dependent protein kinase, that phosphorylates target proteins in the cell.

causing the autism to happen. These proteins occur naturally in our bodies, but they can mutate

ubiquitin-proteasome pathway in normal and disease states. Journal of the American Society of Nephrology. 17,1807-1819.

Experiments and extensive screenings have shown that mutations in FBXW7 are found in approximately 6% of all primary human cancer. T cell acute lymphoblastic leukaemia was the cancer in which exhibited the most frequent mutation of FBXW7. Mouse models have been utilized to further understand the physiological functions of FBXW7 in tumorigenesis. These mice that did not express FBXW7 were analysed and studied especially in the areas of their bone marrow and intestines. Mice with FBXW7 completely knocked out exhibited thymic lymphoma due to the excessive collection of MYC. Biochemical evidence also insinuates that FBXW7 exerts its tumour-suppressant function through the promotion of degradation of various oncoproteins (proteins that promote cancer growth). FBXO11, on the other hand, has shown to target the BCL-6 oncoprotein for ubiquitylation and the following degradation. The overexpression of FBXO11 stopped and inhibited the growth of the cell and induced apoptosis (cell death) by promoting the BCL-6 degradation in large B cell

Moreover, there are many enzymes that participate in the unwinding of the old strands of DNA molecule such as topoisomerase. This enzyme is responsible for initiation of the unwinding of the old strands of DNA molecule. Once supercoiling has been eliminated by the topoisomerase, helicase accomplishes unwinding of the original double strand. In order to aid with the unwinding process, DNA gyrase catalyzes the formation of negative supercoils. The unwound helix, with each strand being synthesized into a new double helix, is called the replication fork.