Oncogenes | Biomolecules | MCAT | Khan Academy
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Oncogenes | Biomolecules | MCAT | Khan Academy

Voiceover: Oncogenes are genes that code for proteins that normally
direct cell growth. They start out as proto-oncogenes and then something happens to convert that proto-oncogene into a full blown oncogene and that’s in some sort
of tumor-inducing agent or it could also be totally spontaneous. Now proto-oncogenes code for proteins that help to regulate cell
growth and differentation which makes sense since
the essence of a tumor, whether it is a cancerous or a benign one, is unregulated cell growth. In fact, the words oncogene and oncology, which is the study of cancer, share the same root word, onkos, which is Greek for mass or bulk. Now the products of these genes are often involved in signal transduction and the execution of mitogenic signals. And you should recall that a mitogen is a chemical substance that encourages a cell to start cell division, basically something that triggers mitosis. So how does a proto-oncogene make that switch into an oncogene? Well, there are three main mechanisms, deletion or point mutation, gene amplification or
increased mRNA stability, and chromosomal rearrangement. So let’s start with the first one. Deletion or point mutation
in coding sequence of the DNA in the gene itself or within a regulatory region such as a promoter region can
lead to either a protein that is produced in
the same normal amounts but is hyperactive for some reason or maybe there’s some
sort of loss of regulation and the normal protein
is just overexpressed. Gene amplification or an
increase in mRNA stability that prolongs the existence of the mRNA and thus its activity
in the cell can lead to a normal protein that is overexpressed. And then finally,
chromosomal rearrangement involves translocation
of a gene to a nearby regulatory sequence that then causes this normal protein, the gene product, to be overexpressed or
you could possibly have fusion to an actively
transcribed gene which overexpresses the fusion protein or leads to a hyperactive fusion protein. And so really you can start to see a theme here emerging where the key idea is that you have either a normal protein
that is just overexpressed, basically too much of the normal protein or you can have normal
expression but the protein itself is just a hyperactive one. Now there are tons of
examples of oncogenes including the SRC oncogene, RAS, MYC, receptor tyrosine kinase, and also cytoplasmic tyrosine kinases. So let’s talk about
each one of those here. SRC was the first confirmed oncogene which was discovered in 1970, and was termed SRC for sarcoma, which is a tumor of mesenchymal cells or connective tissue cells. It was actually an oncogene discovered in a chicken retrovirus and so SRC codes for a nonreceptor protein tyrosine kinase so it phosphorylates specific tyrosine residues and other proteins. Another example of an oncogene is the RAS oncogene, which codes for a small GTPase which hydrolyzes GTP into GDP and phosphate. This protein is activated
by growth factor signaling and functions like a binary switch, sort of an on/off switch, in growth signaling pathways. Examples of downstream effectors of RAS includes the protein
MAPK, which is a type of kinase that in turn regulates genes that mediate cell proliferation. You can see examples of
RAS oncogene mutations In thyroid tumors, certain leukemias, and cancers of the pancreas and colon. The MYC oncogene codes
for a transcription factor that induces cell proliferation and there’s a very common
translocation involving MYC between chromosomes 8, where the MYC oncogene is found, and 14, which leads to a certain type of lymphoma called Burkitt’s lymphoma. The RTK oncogene stands for receptor tyrosine kinase,
which is responsible for adding phosphate groups to other proteins to turn them on or off. These are similar to the SRC gene which is a non-receptor tyrosine kinase, the difference being the
location of the protein, either at the cell surface as a receptor or not as a receptor. So say you have a cell surface receptor that receives a signal
from outside of the cell. Well, then that signal gets
propagated or transmitted Into the cell via these
receptor tyrosine kinases that add phosphate groups
to the target protein, specifically on tyrosine
residues and they can cause cancer by turning
a receptor constitutively or permanently on in the absence of signals from outside the cell. Some well known examples of
receptor tyrosine kinases are vascular endothelial
growth factor or VEGF, epidermal growth factor or EGFR, and platelet derived growth factor, PDGF. And finally we have the
cytoplasmic tyrosine kinases, which mediate responses
to the activation of receptors of cell
proliferation, migration, differentiation, and survival. A well known example is the BCR-ABL gene in chronic myelogenous leukemia or CML, also known as the Philadelphia chromosome. It is a fusion of parts of DNA from chromosome 22 and chromosome 9. So basically a part of chromosome 22 which contains the BCR gene
fuses with a fragment from chromosome 9 which
contains the ABL gene. When these two chromosome fragments fuse, the genes also fuse,
creating this new gene, the BCR-ABL gene. The fused gene codes for
a protein that displays high protein tyrosine kinase activity, which is actually due to
the ABL half of the protein and the unregulated
expression of this protein activates other proteins
that are involved in cell cycle and cell
division which causes a cell to grow and divide uncontrollably, basically becoming cancerous. So as a result, the
Philadelphia chromosome is associated wtih chronic
myelogenous leukemia, a certain type of leukemia
as I mentioned before, as well as other forms of leukemias, which are cancers of white blood cells.

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34 thoughts on “Oncogenes | Biomolecules | MCAT | Khan Academy

  1. Not convinced that proto-oncogenes can be activated by deletion (1.36). Point mutation yes, but only mis-sense mutations. Not single bp deletions, or gene deletions. That would be tumour suppressor inactivation.

  2. One question, if you´re talking about receptors It should not be <<VEGFR instead of VEGF>> and <<PDGFR instead of PDGF>>?

  3. Think you are explaining this to a beginner with basic biology.there is presumption of too much knowledge and sounds like an explanation of what you know rather than how to make beginners understand .Think basic,

  4. Writing an assignment for 2nd year Biomed and this is waaaay too fast to keep up with, not enough written down on the slides and having to pause and rewind every second sentence.

  5. Good information but it seems like she in rushing to go somewhere because i had playback quite often.

  6. This video is very informative and made very simple to understand. It's not that hard to follow and video is short and straight to the point. If you don't like to rewind don't watch the video or just deal with it.

    LEGALLY BLOND TYPE OF ACCENT, god I´m blessed not live in America

  8. Great video, really if you think this is too quick/advanced you need to realize

    1) If you don't get it on your first run that is NORMAL- if you have gotten to this level it is supposed to be hard.
    2) it is not important that every single enzyme/kinase/transcription factor and every little three letter acronym you know right away, but that you just try to follow.
    3) you should be grateful that this video exists in the first place because ten years ago you would have had to reread a textbook until you got it which is much more laborious than watching this a few times.

  9. Nice explanation but my fucking godd stop it with that fake kardashion scarring shit of your voice, sounds absolutely ridiculous and is annoying af

  10. I don't get what's with people and their nasty comments, but I really appreciate this video. I'm doing my final year project, and it's something to do with cancer and I have 0 shits about what's going on. Thanks for the basics 😀

  11. So is the point of the video is that Oncogenes are genes that typically are responsible for cell growth, and something get fucked up through one of the 3 listed ways, they become cancerous?

    Were 3000 examples of oncogenes really necessary? There no way one can be expected to know that level of detail

  12. Absolutely not an introductory-level presentation of Oncogenes. You sound like you're reading off of an oncology publication. & for the love of god please stop dragging out your words, "ooooof" "aaaaaand" "theeeee".

  13. Can we get a video on lethal alleles with some problems to work out 😇 and please include different scenarios ‼️

  14. I REALLY don't get why people are being so nasty on this video :/ Studying for my Biochem 2 Exam in Med school and this is perfect as a little overview of oncogenes – we do need to know a bit more detail concerning those mentioned, so definitely not too quick/hard for what I'm studying. Obviously different people watching this are all coming from different backgrounds, but you can't honestly expect one lecture to cater to anyone wether they are studying biochemistry at an advanced level or just coming out of high school or whatever…

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