Name: how cdk inhibitors slow cell division
Uploaded: 2023-04-30T18:28:50.000Z
Duration: 2 min 34 s
Channel: JoVE

K12 Standards

Pennsylvania State Academic Standards

9-12

Life Science

Inheritance and Variation of Traits

3.1.9-12.D

Inhibition of CDK Activity

During cell cycle transitions, Cdk activity is regulated by multiple proteins, ensuring controlled cell growth, complete DNA replication, and mitotic distribution of the chromosomes to daughter cells.
In the absence of regulatory proteins, an abnormal cell goes unchecked, leading to conditions such as cancer.
In a normal cell, Cdk activity is regulated through multiple mechanisms including cyclin degradation, inhibitory phosphorylation, and inhibitory conformational changes induced by Cdk inhibitor binding.
Cyclin levels are known to fluctuate during the cell cycle. Cdks are only active when bound to cyclin, therefore, cyclin degradation leaves Cdks inactive and unable to promote the transition to the next cell cycle stage.
In another mechanism, a kinase named Wee1, phosphorylates the active site in Cdk.&#160; This phosphorylation inhibits the activity of the cyclin-Cdk complex.
Additionally, Cdk inhibitors or CKIs, such as p16, p21, and p27, regulate Cdk activity through inhibitory conformational changes.
For instance, if DNA damage occurs during G1, p16 interacts with the cyclin-Cdk complex. This interaction causes a large structural rearrangement, detaching the bound cyclin, causing Cdk inactivation.&#160;
DNA damage in the G1 phase can also trigger the tumor suppressor protein, p53, to activate p21.
G1/S-Cdk and S-Cdk complexes are bound and inhibited by p21, arresting the cells in the G1 phase, and allowing enough time for DNA repair.
For the G1/S phase transition to take place, the cell is required to have all the resources needed for DNA replication. If the cell lacks the necessary resources, p27 binds to G1/S-Cdk and S-Cdk complexes, inhibiting the enzyme activity.
Once favorable conditions for cell cycle progression are met, p27 is degraded, restoring Cdk activity and promoting cell transition.

inhibition of cdk activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex then phosphorylates and inactivates the tumor suppressor retinoblastoma protein (Rb) to promote the G1-to-S phase transition of the cell cycle. In normal cells, Rb protein is reactivated through the regulation of Cdk activity, thus, preventing abnormal cell cycle transitions. 
There are at least three known mechanisms by which Cdk activity is regulated- cyclin degradation, inhibitory phosphorylation, or binding of inhibitory proteins. Mutations that prevent these mechanisms lead to Cdk-mediated tumorigenesis.
Because Cdk 4/6 plays a substantial role in tumor formation, several Cdk inhibitors have been developed for clinical use. The most recent ones are selective for Cdk4 and Cdk6. There are at least three clinically approved Cdk 4/6 inhibitors: abemaciclib, ribociclib, and palbociclib. These inhibitors bind to the ATP pocket of Cdk 4 and 6, inactivating the Cyclin D-Cdk4/6 complexes, leading to Rb protein activation and subsequent cell cycle arrest. In some cases, the inhibitor-mediated cell cycle arrest causes an increase in apoptosis in tumor cells.
Inhibition of the cell cycle and subsequent programmed cell death are the most common mechanisms of Cdk4/6 inhibitors. However, a recent study in mouse models of breast cancer showed that Cdk4/6 inhibition could also lead to severe immunogenic effects. During the study, the Cdk inhibitor seemed to enhance tumor cells&#39; antigen-presenting ability, thereby allowing cytotoxic T cells to recognize and destroy the tumor cells.

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be ...

Education

JoVE Core

Cell Biology

Unit 1

Cell Proliferation

KEY TERMS AND CONCEPTS

how cdk inhibitors slow cell division

Cyclin-dependent kinase (CDK) inhibitors slow cell division by blocking CDK activity. CDKs are enzymes that help control the cell cycle, which is the series of steps a cell follows to grow and divide. When CDKs are inhibited, the cycle can pause instead of moving forward.

The video focuses on this control point in cell growth. CDK inhibition is important because it helps regulate when cells enter the next stage of the cycle. By stopping CDK activity, cells do not continue dividing at the wrong time.

This topic is useful for understanding how cells are kept under control during normal growth. It also shows how a single regulatory step can affect the whole cell cycle. In high school biology, CDK inhibitors are a key example of how enzymes and cell division are linked.

How CDK Inhibitors Slow Cell Division

what is the cell cycle?

Cell Cycle Stages and Checkpoints

The cell cycle is the set of events that a typical eukaryotic cell goes through during its life. In somatic cells, it has two main stages: interphase and the mitotic phase. Interphase is the time when the cell grows, carries out basic metabolic functions, copies its DNA, and gets ready to divide. The mitotic phase comes next. During mitosis, the nucleus divides, and during cytokinesis, the cytoplasm divides. These steps produce two daughter cells that are identical to the original parent cell.

interphase

Cell Growth Phases Before Mitosis

Interphase is the part of the cell cycle when a eukaryotic cell grows and gets ready for mitosis. In a typical human cell, the full cell cycle lasts about 24 hours. Interphase makes up about 95 percent of that time and includes three stages: G1, S, and G2. After mitosis and cytokinesis, cells enter G1, or gap 1. During this stage, cells grow continuously and prepare for DNA replication. They are metabolically active and copy important organelles and biochemical molecules, including proteins. <br...

the cell cycle control system

Cell Cycle Checkpoints and Regulation

The cell cycle is controlled by checkpoints and regulator proteins that help cells divide in an orderly way. These controls monitor whether a cell is ready to move from one stage to the next. They help prevent division from continuing when conditions are not right. The control system depends on proteins that can either encourage or block progress through the cycle. Some of these regulators act as signals that push the cell forward. Others act as brakes that slow the cycle when problems are...

positive regulator molecules

Positive Regulators in Cell Growth

Positive regulator molecules help cells move through the cell cycle. The cell cycle is the series of steps a cell uses to grow and divide. These molecules act as signals that support progress through each stage. Two important examples are cyclins and cyclin-dependent kinases, or CDKs. Cyclins are proteins that rise and fall during the cell cycle. CDKs are enzymes that work with cyclins to help control cell-cycle events. Together, these positive regulators help the cell advance when conditions...

Cyclin-dependent kinase (CDK) inhibitors slow cell division by blocking CDK activity. CDKs are enzymes that help control the cell cycle, which is the series of steps a cell follows to grow and divide. When CDKs are inhibited, the cycle can pause instead of moving forward. The video focuses on this control point in cell growth. CDK inhibition is important because it helps regulate when cells enter the next stage of the cycle. By stopping CDK activity, cells do not continue dividing at the wrong...

s-cdk initiates dna replication

S-Cdk Starts the DNA Copying Process

S-Cdk starts the DNA copying process by triggering DNA replication. S-Cdk is a cyclin-dependent kinase that helps move the cell into S phase, the part of the cell cycle when DNA is copied. This step matters because the cell must begin replication at the right time. S-Cdk adds phosphate groups to target proteins, which changes their activity and helps turn on the machinery needed for DNA synthesis. The result is that replication can begin in a controlled way. This process is an important part...

m-cdk drives transition into mitosis

M-Cdk Triggers the Start of Mitosis

M-Cdk triggers the start of mitosis by helping a cell move from interphase into division. It is a key cell-cycle regulator that turns on the mitotic program at the right time. The M-Cdk complex includes a cyclin and a cyclin-dependent kinase. When this complex becomes active, it sends signals that push the cell into mitosis. This step helps control when chromosomes begin to condense and the nuclear changes of division can begin. Understanding M-Cdk is important because it links cell-cycle...

mitogens and the cell cycle

Mitogen Signals in Cell Division

Mitogens are signals that help cells move through the cell cycle. The cell cycle is the set of stages a cell follows to grow and divide. In many cells, mitogens are needed before the cell can enter division. These signals work through pathways inside the cell. One important route is the MAP kinase signaling pathway, which helps pass the mitogen message from the cell surface to the cell’s interior. This signaling helps the cell respond and continue through the cycle. Mitogens are closely tied...

replicative cell senescence

Telomere Shortening and Cell Aging

Replicative cell senescence is a form of cell aging linked to repeated cell division. As cells divide, their telomeres shorten. Telomeres are protective DNA caps at the ends of chromosomes. When telomeres become too short, cells can no longer keep dividing in the same way. The cell enters senescence, a state in which it stays alive but stops dividing. This process helps explain how division limits can affect cell growth over time.

abnormal proliferation

Unchecked Cell Growth Patterns

Abnormal proliferation is a pattern of cell growth that does not follow normal control. In healthy tissue, cells divide only when they are needed. When that control is lost, cells can keep multiplying in an unusual way. This kind of cell growth can be seen in different settings. It may involve cells that divide too fast, too often, or when they should stop. The result is tissue that grows in a way that no longer matches the body’s normal balance. Understanding abnormal proliferation helps...

cells coordinate growth and proliferation

cells-coordinate-growth-and-proliferation

Cell Size Homeostasis and Checkpoints

Cells coordinate growth and proliferation to keep cell size under control. Growth increases cell mass, while proliferation creates new cells. Together, these processes help cells maintain size homeostasis, which means keeping a stable size over time. The cell cycle includes a checkpoint called the size checkpoint. At this point, the cell checks whether it has grown enough before it divides. This control helps connect growth with cell division, so cells do not become too small or too large. <br...

key terms and concepts

Learn how CDK inhibitors block cyclin-dependent kinase activity and slow the cell cycle. A clear high school explanation of cell division control.

How CDK Inhibitors Slow Cell Division | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Louisiana Student Standards for Science

High School

Life Sciences

from-molecules-to-organisms-structures-and-processes

From Molecules To Organisms: Structures And Processes

HS-LS1-4

Tennessee Academic Standards

Biology

From Molecules to Organisms: Structures and Processes

BIO1.LS1.6

Minnesota Academic Standards in Science

3.1.1 9L.3.1.1.2

new-jersey-student-learning-standards-for-science

New Jersey Student Learning Standards for Science

Arizona Science Standards

HS.L1

HS.L1U1.22

Alabama Course of Study Science

9-12.B.1.3

Florida Department of Education

SC.912.L.16

SC.912.L.16.8

What is the Cell Cycle?

The cell cycle refers to the sequence of events occurring throughout a typical cell&#8217;s life. In eukaryotic cells, the somatic cell cycle has two ...

Interphase

The cell cycle occurs over approximately 24 hours (in a typical human cell) and in two distinct stages: interphase, which includes three phases of the ...

The Cell Cycle Control System

Positive Regulator Molecules

Mitosis and Cytokinesis

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Chromosome Duplication

Cohesins

Condensins

The Mitotic Spindle

Centrosome Duplication

Spindle Assembly

Attachment of Sister Chromatids

Forces Acting on Chromosomes

Separation of Sister Chromatids

The Spindle Assembly Checkpoint

Anaphase A and B

Anaphase Promoting Complex

The Contractile Ring

Determining the Plane of Cell Division

The Phragmoplast

Distribution of Cytoplasmic Content

An Introduction to Cell Division

Cell division is the process by which a parent cell divides and gives rise to two or more daughter cells. It is a means of reproduction for single-cell ...

Cell Cycle Analysis

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Live Cell Imaging of Mitosis

Mitosis is a form of cell division in which a cell&#8217;s genetic material is divided equally between two daughter cells. Mitosis can be broken down into ...

Fertilization

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Cleavage and Blastulation

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Gastrulation

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Neurulation

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Cell Migration

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An Introduction to Developmental Genetics

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An Introduction to Organogenesis

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Students who demonstrate understanding can use a model to illustrate the role of cellular division (mitosis) and differentiation in producing and maintaining complex organisms.  Assessment Boundary: Assessment does not include specific gene control mechanisms or rote memorization of the steps of mitosis.

DNA Packaging

DNA as a Genetic Template

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Organization of Genes

Structure of a Gene

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Chromosome Structure

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Chromosome Replication

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The Nucleosome

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Chromatin Packaging

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Karyotyping

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Genome Size and the Evolution of New Genes

Gene Families

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3.1.9-12.P

Genomic DNA in Prokaryotes

The genome of most prokaryotic organisms consists of double-stranded DNA organized into one circular chromosome in a region of cytoplasm called the ...

Binary Fission

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Genomic DNA in Eukaryotes

Eukaryotes have large genomes compared to prokaryotes. To fit their genomes into a cell, eukaryotic DNA is packaged extraordinarily tightly inside the ...

What is Meiosis?

Meiosis is the process by which diploid cells divide to produce haploid daughter cells. In humans, each diploid cell contains 46 chromosomes, half from ...

Meiosis I

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Meiosis II

Meiosis II is the second and final stage of meiosis. It relies on the haploid cells produced during meiosis I, each of which contain only 23 ...

Crossing Over

Unlike mitosis, meiosis aims for genetic diversity in its creation of haploid gametes. Dividing germ cells first begin this process in prophase I, where ...

Nondisjunction

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Base-pairing and DNA Repair

The DNA Replication Fork

Lagging Strand Synthesis

The Replisome

Proofreading

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Replication in Prokaryotes

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Replication in Eukaryotes

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Telomeres and Telomerase

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Types of Genetic Transfer Between Organisms

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Students who demonstrate understanding can make and defend a claim based on evidence that inheritable genetic variations may result from (1) new genetic combinations through meiosis, (2) viable errors occurring during replication, and/or (3) mutations caused by environmental factors. Assessment Boundary: Assessment does not include the phases of meiosis or the biochemical mechanism of specific steps in the process.

3.1.9-12.Q

What is Population Genetics?

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3.1.9-12.R

How CDK Inhibitors Slow Cell Division

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