Name: ras and myc in uncontrolled cell growth
Uploaded: 2021-04-07T12:12:01.000Z
Duration: 2 min 23 s
Channel: JoVE

&#160;Cells have special genes called tumor suppressor genes that can neutralize the effect of harmful genetic alterations and prevent uncontrolled cell proliferation.
For example, p53 is a tumor suppressor gene that maintains a basal level of expression under normal cell conditions.
Mdm2 protein acts as a negative regulator of p53 activity. It binds to the functional domain of p53 protein, reducing its transcriptional activity.
Mdm2 also exhibits p53-specific ubiquitin ligase activity and catalyzes the attachment of ubiquitin to p53. The polyubiquitinated p53 proteins are then recognized and degraded by the proteasome, maintaining it at extremely low levels inside the cell.
However, when the cells encounter abnormal conditions such as cellular stress or excessive mitogenic stimulation, the p53 gene is induced to enforce its tumor suppression activity.
For instance, overexpression of transcription factor Myc in the nucleolus triggers the accumulation of a tumor suppressor protein called- Arf.
Arf directly binds to Mdm2, inhibiting its ubiquitin ligase activity and sequestering it in the nucleolus, thus releasing active p53 into the nucleoplasm.
Active p53 then binds to specific DNA sequences and induces the expression of its target genes that can trigger accelerated DNA repair, arrest cell cycle, or induce cell apoptosis, thus, preventing further propagation of damaged cells.
&#160;However, when genetic or epigenetic changes alter p53 activity, it results in the collapse of the cell&#8217;s protective mechanisms. Such cells start proliferating aggressively and form tumors.
Besides, overexpression of Mdm2 is also frequently observed in liposarcomas.&#160; Although such tumors retain the normal p53 gene, the increased levels of Mdm2 keep p53 in an inactive state, hence, restricting their tumor suppression activity.

abnormal proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell&#39;s growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter cells and all the future daughter cells. Such abnormal cell proliferation defines the characteristic of what we call cancer. The best example to explain this condition is the mutation in the Ras and MYC proteins.
Normal Ras proteins are GTPases that function in signal transduction from cell surface receptors to the cell&#8217;s interior. Ras proteins can be denoted as the binary switches that cycle between ON and OFF states during cellular growth. Usually, these switches are tightly regulated, but in Ras-related diseases such as cancer, the Ras gene mutation or their regulator renders Ras proteins persistently active. For instance, a single amino acid missense mutation in the K-Ras protein (a type of Ras protein) impairs its normal functioning. The mutant K-Ras cannot be inactivated, leading to continuous growth stimulation. K-Ras mutation occurs in 15%- 20% of human cancers, and is most commonly seen in colon cancer, lung cancer, pancreatic cancer, and leukemia.
Abnormal cell proliferation can also occur when mutation results in overexpression of MYC protein. The MYC oncogene belongs to a family of &#34;super-transcription factors&#34; and is deregulated in more than 50% of human cancers. The MYC affects a spectrum of cellular functions, including protein translation, cell cycle progression, ribosome biosynthesis, cell proliferation, differentiation, survival, and immune surveillance.

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. ...

Education

JoVE Core

Molecular Biology

Unit 2

Cell Proliferation

KEY TERMS AND CONCEPTS

ras and myc in uncontrolled cell growth

Ras and MYC can drive abnormal cell proliferation, which is uncontrolled cell growth. Under normal conditions, most adult cells stay non-proliferative unless they receive internal or external signals to replace lost cells. In abnormal proliferation, cell division continues even after those signals stop. This persistent growth can lead to tumors.

The tumor forms from damaged cells that keep copying themselves. Those cells pass the damage to daughter cells and to later generations of daughter cells. Over time, this abnormal growth becomes a key feature of cancer.

One example involves Ras proteins. Normal Ras proteins are GTPases, which are enzymes that help move signals from cell surface receptors into the cell interior. They work like binary switches that turn ON and OFF during cell growth. In cancer, a mutation in the Ras gene or in a protein that regulates Ras can leave the switch stuck in the ON state.

A single amino acid missense mutation in K-Ras, a type of Ras protein, can disrupt normal function. The mutant K-Ras cannot be turned off, so it keeps stimulating growth. K-Ras mutations are seen in about 15% to 20% of human cancers. They are most often found in colon cancer, lung cancer, pancreatic cancer, and leukemia.

MYC can also cause abnormal cell proliferation when it is overexpressed. MYC is an oncogene and belongs to a family of super-transcription factors. It is deregulated in more than 50% of human cancers. MYC affects many cell functions, including protein translation, cell cycle progression, ribosome biosynthesis, cell proliferation, differentiation, survival, and immune surveillance.

Ras and MYC in Uncontrolled Cell Growth

what is the cell cycle?

Cell Growth and Division in the Cell Cycle

The cell cycle is the process that cells use to grow and divide. It helps living things make new cells for growth and repair. In many cases, it is also the way single cells reproduce. The cycle has two main parts: interphase and cell division. During interphase, the cell grows and prepares for division. During cell division, one cell splits into new cells. This sequence keeps cells in a repeating pattern of growth, copying, and splitting.

interphase

Interphase in the Cell Cycle

Interphase is the part of the cell cycle when a cell grows and prepares to divide. It is a major stage in the life of a cell, and it includes the phases G1, S, and G2. During G1, the cell grows and carries out its normal functions. In the S phase, the cell copies its DNA. During G2, the cell continues to grow and gets ready for mitosis, the stage when the cell divides. Interphase takes up most of the cell cycle. It gives the cell time to build materials, make a copy of its genetic...

the cell cycle control system

How Cell Division Is Controlled

The cell cycle is the organized process that controls cell division. It helps one cell divide into two daughter cells with chromosomes that match the parent cell. This process is essential for growth from a single-cell zygote and for tissue renewal in adult multicellular eukaryotes. Cell division also supports repair and replacement in the body. In bone marrow, stem cells divide to make new blood cells. When cell division happens without control, it can lead to cancer and many genetic diseases.

positive regulator molecules

Cyclins and Cdks in Cell Cycle Control

Cyclins and cyclin-dependent kinases help control how cells move through the cell cycle. These positive regulator molecules keep mitotic cell division on schedule so daughter cells can match the parent cell. When this control fails, errors in DNA replication or in the distribution of genetic material can create mutant cells that pass those changes to every new cell they form. Cell cycle checkpoints limit the spread of these abnormal cells. A checkpoint is a control point at a specific stage of...

inhibition of cdk activity

Cdk4/6 Blockers and Cell Cycle Control

Cdk4/6 blockers help control the cell cycle by stopping the signals that push cells from G1 into S phase. Cdks, or cyclin-dependent kinases, must bind cyclins to become active, and cyclin D often pairs with Cdk4/6 to form this active complex. The cyclin D-Cdk4/6 complex then phosphorylates the retinoblastoma protein, or Rb, which normally acts as a tumor suppressor. When Rb is inactivated, cells can move into the next stage of division. In normal cells, Cdk activity is carefully regulated so...

s-cdk initiates dna replication

Cdk Control of DNA Replication Timing

Cdk control of DNA replication timing helps cells copy DNA once each cycle. The cell cycle has four main stages: G1, S, G2, and M. In G1, the cell grows. In S phase, it copies its DNA. In G2, it prepares to divide. In M phase, mitosis divides the cell content into two daughter cells. In eukaryotes, DNA replication starts at many sites on the chromosomes called origins of replication. These origins switch between two states during the cell cycle. In G1, a multiprotein pre-replicative complex,...

m-cdk drives transition into mitosis

Cell Cycle Kinases Trigger Entry into Mitosis

Cell cycle kinases help control the move from G2 into M phase. Checkpoints act as safeguards and gatekeepers, so the cell cycle can continue in good conditions and slow down or stop when problems appear. This regulation is called the cell cycle control system. Cyclin-dependent kinases, or Cdks, work with cyclins to manage cell cycle transitions. A key example is M-Cdk, which is made of Cdk1 bound to M cyclin. M-Cdk helps drive the shift from G2 to M phase by preparing the cell for mitosis. M...

mitogens and the cell cycle

EGF Signaling and Cancer Cell Growth

Epidermal growth factor, or EGF, is a mitogen that helps control cell division. Its receptor, EGFR, sits in the cell membrane and sends a growth signal when EGF binds to it. EGFR is part of the ErbB family of tyrosine kinase receptors, and this signaling helps decide whether a cell will keep proliferating. In healthy tissue, the number of EGFR molecules on the cell surface is tightly regulated. This balance helps cell division match the tissue’s needs. In cancer cells, however, EGFR is often...

replicative cell senescence

Telomeres, Telomerase, and Tumor Control

Telomeres and telomerase help control how many times a cell can divide. Telomeres are short, repetitive DNA sequences at the ends of chromosomes. They are covered by proteins that form a protective cap. In many human body cells, this cap gets a little shorter after each round of cell division. This shortening is part of replicative senescence, the point at which a cell stops dividing permanently. Embryonic stem cells make telomerase, an enzyme that adds telomeric repeats and supports repeated...

Ras and MYC can drive abnormal cell proliferation, which is uncontrolled cell growth. Under normal conditions, most adult cells stay non-proliferative unless they receive internal or external signals to replace lost cells. In abnormal proliferation, cell division continues even after those signals stop. This persistent growth can lead to tumors. The tumor forms from damaged cells that keep copying themselves. Those cells pass the damage to daughter cells and to later generations of daughter...

cells coordinate growth and proliferation

cells-coordinate-growth-and-proliferation

Cell Size Control in Growth and Muscle

Cell size control helps cells keep their shape, function, and fitness. Many dividing cells grow and then double their mass before they divide. This coordination depends on checkpoints between cell cycle phases, which help the cell stay in balance. When checkpoint control fails, cells may grow without proper control. That loss of coordination can lead to uncontrolled growth and reduced cellular function. In adult tissues, non-dividing cells also adjust size based on metabolic state. Adult...

key terms and concepts

Learn how Ras mutations and MYC overexpression can keep cells dividing, form tumors, and contribute to cancer in high school biology.

Ras and MYC in Uncontrolled Cell Growth | JoVE K12

molecular biology

JoVE Core Molecular Biology showcases the molecular processes of the cell through clear and concise animated video lessons. Additionally, in scientist-in-action videos, these concepts' application is demonstrated through real experiments in modern laboratories.

Ras and MYC in Uncontrolled Cell Growth

Description

Transcript

Tags