10.3 Control of the Cell Cycle
3 min read•june 14, 2024
The cell cycle is a tightly regulated process that ensures proper cell division. Cells progress through distinct phases, each controlled by specific proteins and checkpoints. These mechanisms safeguard against errors and maintain genomic stability.
and () are key players in cell cycle regulation. They work together to drive cells through different stages, while checkpoints act as quality control. External factors like growth signals and nutrient availability also influence cell division.
Cell Cycle Regulation
Regulation of cell cycle
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- Internal factors regulate cell cycle progression from within the cell
- and cyclin-dependent kinases (CDKs) control cell cycle transitions
- Cyclins bind to and activate CDKs which then phosphorylate target proteins
- Different cyclin-CDK complexes are active at specific stages (G1, S, G2, M)
- () monitor DNA integrity
- Monitor DNA damage and can halt cell cycle if damage is detected to allow for repair
- () promote cell division when activated by growth signals
- Can become oncogenes if mutated or overexpressed leading to uncontrolled cell division (cancer)
- and cyclin-dependent kinases (CDKs) control cell cycle transitions
- External factors regulate cell cycle progression from outside the cell
- Growth factors () stimulate cell division
- Bind to cell surface receptors and promote progression through
- Cell density influences cell division through
- Cells stop dividing when they reach a certain density and touch neighboring cells
- requires most cells to attach to a surface to divide
- on cell surface bind to extracellular matrix components
- Nutrient availability (glucose, amino acids) is required for cell division
- Sufficient nutrients are required for energy production and biosynthesis
- Growth factors () stimulate cell division
Key cell cycle checkpoints
- () ensures cell is ready to enter
- Checks for adequate cell size, nutrient availability, and absence of DNA damage
- ensures DNA replication is complete and accurate
- Checks for DNA damage and proper chromosome alignment before
- () ensures proper chromosome attachment
- Prevents anaphase onset until all kinetochores are properly attached to spindle microtubules
- is activated once all chromosomes are properly aligned
- Significance of checkpoints in maintaining genomic stability
- Prevent cell cycle progression if conditions are not met (cell size, DNA integrity)
- Allow for repair of DNA damage or other cellular issues before proceeding to next phase
Cyclins and cyclin-dependent kinases
- Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases
- Phosphorylate target proteins to regulate their activity
- Require binding of cyclins for activation
- Cyclins are regulatory subunits that bind to and activate CDKs
- Levels fluctuate throughout the cell cycle (synthesized and degraded)
- Cyclin-CDK complexes regulate specific cell cycle transitions
- G1/S cyclins () and CDKs (, ) promote entry into S phase
- Phosphorylate releasing transcription factor E2F
- E2F activates genes required for DNA replication in S phase
- S phase cyclins () and CDKs () promote DNA replication and S phase progression
- cyclins () and CDKs () promote entry into mitosis
- Phosphorylate substrates involved in nuclear envelope breakdown, chromosome condensation, and spindle assembly
- are duplicated and separated to form the mitotic spindle poles
- G1/S cyclins () and CDKs (, ) promote entry into S phase
- Regulation of cyclin-CDK activity by inhibitors and proteolysis
- Cyclin-dependent kinase inhibitors () like and bind to and inhibit cyclin-CDK complexes
- Ubiquitin-mediated proteolysis degrades cyclins by the proteasome
- Allows for rapid inactivation of cyclin-CDK complexes at specific points in the cell cycle
Cell cycle phases and cellular processes
- consists of G1, S, and G2 phases where cells grow and prepare for division
- Mitosis (M phase) is the process of nuclear division
- is the process of cytoplasmic division following mitosis
Cell cycle exit and cellular fates
- is programmed cell death that can occur in response to severe DNA damage or other cellular stresses
- is a state of permanent cell cycle arrest that can be triggered by telomere shortening or cellular stress
Key Terms to Review (52)
Acetylcholinesterase: Acetylcholinesterase is an enzyme that breaks down the neurotransmitter acetylcholine in the synaptic cleft. It plays a crucial role in terminating synaptic transmission and allowing muscle relaxation.
Anaphase-promoting complex (APC): The anaphase-promoting complex (APC) is a crucial protein complex that plays a key role in regulating the cell cycle, particularly during the transition from metaphase to anaphase. It functions as an E3 ubiquitin ligase, tagging specific proteins for degradation, which ensures the proper separation of chromosomes and progression through the cell cycle. By controlling the degradation of proteins like cyclins and securin, the APC helps maintain the order and timing of cell division.
Anchorage Dependence: Anchorage dependence is the requirement of cells to be attached to a substrate or surface in order to grow and divide. This characteristic plays a crucial role in regulating the cell cycle and ensuring that cells only proliferate when in the proper environment, helping to prevent uncontrolled growth and maintaining tissue integrity.
APC/C: APC/C, or Anaphase-Promoting Complex/Cyclosome, is a multi-subunit E3 ubiquitin ligase that plays a crucial role in the regulation of the cell cycle. It functions by tagging specific proteins for degradation, ensuring that cells progress through key transitions such as anaphase and mitosis. By targeting cyclins and other regulatory proteins, APC/C helps maintain proper timing and order of cell division, which is vital for cell health and function.
Apoptosis: Apoptosis is a programmed cell death process that occurs in multicellular organisms, characterized by a series of tightly regulated events leading to the elimination of unwanted or damaged cells. This mechanism is crucial for maintaining tissue homeostasis, regulating the cell cycle, and ensuring proper development and functioning of organisms.
CDK1: CDK1, or Cyclin-Dependent Kinase 1, is a crucial enzyme that regulates the cell cycle, particularly the transition from G2 phase to M phase (mitosis). It is activated by binding to cyclins, specifically cyclin B, and plays a key role in orchestrating the events necessary for cell division. The proper functioning of CDK1 ensures that cells can divide accurately and at the right time, maintaining genomic integrity and cellular homeostasis.
CDK2: CDK2, or Cyclin-Dependent Kinase 2, is an important protein kinase that plays a crucial role in regulating the cell cycle, particularly in the transition from the G1 phase to the S phase. It partners with cyclins, primarily cyclin E and cyclin A, to drive the cell cycle forward by phosphorylating target proteins, which leads to the progression of cellular events necessary for DNA replication and cell division.
CDK4: CDK4, or Cyclin-Dependent Kinase 4, is an important enzyme that plays a crucial role in regulating the cell cycle, specifically the transition from the G1 phase to the S phase. This kinase partners with cyclins to phosphorylate target proteins, facilitating cell cycle progression. In the context of cancer, CDK4 can become dysregulated, leading to uncontrolled cell division and tumor growth.
CDK6: CDK6, or Cyclin-Dependent Kinase 6, is a crucial protein that plays a key role in regulating the cell cycle, particularly the transition from the G1 phase to the S phase. This kinase interacts with cyclins to drive cell proliferation and is essential for the proper progression of cells through the cell cycle. Additionally, alterations in CDK6 activity can lead to uncontrolled cell division and are implicated in various cancers, highlighting its importance in gene regulation and cancer biology.
CDKs: Cyclin-dependent kinases (CDKs) are a family of protein kinases that play a crucial role in regulating the cell cycle by phosphorylating specific target proteins. They are activated when bound to cyclins, which are proteins that fluctuate in concentration throughout the cell cycle. CDKs ensure the proper timing and progression of the cell cycle, making them essential for normal cell division and functioning.
Cell senescence: Cell senescence is a state in which a cell ceases to divide and grow, often as a response to stress or damage, and enters a permanent growth arrest. This phenomenon is essential for preventing the proliferation of damaged cells, thus playing a critical role in maintaining tissue health and regulating the cell cycle.
Cell-cycle checkpoints: Cell-cycle checkpoints are regulatory pathways that ensure the proper progression of the cell cycle. They prevent the cycle from advancing to the next phase until specific conditions are met, ensuring genomic integrity and cellular function.
Centrosomes: Centrosomes are cellular structures that serve as the main organizing centers for microtubules and play a crucial role in cell division. They consist of a pair of centrioles surrounded by a matrix of proteins and are essential for the formation of the mitotic spindle, which helps separate chromosomes during mitosis. By regulating microtubule organization, centrosomes ensure proper cell cycle progression and division.
CKIs: CKIs, or Cyclin-Dependent Kinase Inhibitors, are proteins that play a crucial role in regulating the cell cycle by inhibiting the activity of cyclin-dependent kinases (CDKs). These inhibitors help ensure that the cell cycle progresses at the right pace and can halt the cycle in response to DNA damage or other cellular stresses, promoting proper cell division and preventing uncontrolled growth.
Contact inhibition: Contact inhibition is a regulatory mechanism that stops cells from dividing when they come into contact with one another. This process plays a crucial role in maintaining tissue architecture and preventing uncontrolled cell growth, which is essential for normal cellular function and homeostasis.
Cyclin A: Cyclin A is a regulatory protein that plays a crucial role in controlling the progression of the cell cycle, specifically during the S phase and the G2 phase. It forms a complex with cyclin-dependent kinases (CDKs), particularly CDK2, which helps to phosphorylate target proteins necessary for DNA replication and cell division. This interaction is essential for ensuring that the cell properly prepares for mitosis, maintaining genomic stability and proper cellular function.
Cyclin B: Cyclin B is a regulatory protein that plays a crucial role in controlling the cell cycle, specifically in the transition from the G2 phase to the M phase (mitosis). It partners with cyclin-dependent kinase 1 (CDK1) to form the cyclin B-CDK1 complex, which is essential for triggering various processes that prepare the cell for mitosis. This complex helps to ensure that the cell has properly replicated its DNA and is ready to divide.
Cyclin D: Cyclin D is a regulatory protein that plays a crucial role in controlling the cell cycle, specifically in the transition from the G1 phase to the S phase. It acts by activating cyclin-dependent kinases (CDKs), which are essential for driving the cell through key checkpoints in the cell cycle, responding to growth signals and regulating cellular proliferation.
Cyclin D-CDK4: Cyclin D-CDK4 is a protein complex that plays a crucial role in regulating the cell cycle, specifically in the transition from the G1 phase to the S phase. This complex is formed when cyclin D binds to cyclin-dependent kinase 4 (CDK4), which activates CDK4's kinase activity. The cyclin D-CDK4 complex phosphorylates target proteins that promote cell cycle progression, linking growth signals to the cell's ability to divide and replicate.
Cyclin E-CDK2: Cyclin E-CDK2 is a complex formed by the regulatory protein cyclin E and the cyclin-dependent kinase CDK2, crucial for the control of the cell cycle, particularly in the transition from the G1 phase to the S phase. This complex drives the progression into DNA synthesis by phosphorylating target proteins that facilitate cell cycle progression, thereby ensuring that cells only replicate their DNA when they are ready.
Cyclin-dependent kinases: Cyclin-dependent kinases (CDKs) are a family of protein kinases that play a crucial role in regulating the cell cycle by phosphorylating specific target proteins when activated by binding to cyclins. This interaction is vital for the progression through different phases of the cell cycle, including DNA replication and mitosis, making them key players in cellular division and growth.
Cyclins: Cyclins are proteins that regulate the progression of the cell cycle by activating cyclin-dependent kinases (CDKs). They ensure that cell cycle events occur in the correct sequence and at the appropriate time.
Cyclins: Cyclins are a family of proteins that play a crucial role in regulating the cell cycle by activating cyclin-dependent kinases (CDKs). These proteins are essential for transitioning between different phases of the cell cycle, ensuring that cellular processes such as DNA replication and cell division occur in a timely and orderly manner. Cyclins are synthesized and degraded in a cyclical pattern, reflecting their name, which is critical for the precise control of cell division.
Cytokinesis: Cytokinesis is the process that follows cell division, where the cytoplasm of a parent cell is divided into two daughter cells, completing the overall cell division. This process is crucial for ensuring that each daughter cell receives a full set of organelles and sufficient resources to function effectively after mitosis or meiosis.
Epidermal growth factor: Epidermal growth factor (EGF) is a protein that stimulates cell growth, proliferation, and differentiation by binding to its receptor, EGFR. It plays a vital role in various biological processes, including wound healing and tissue regeneration, and is critical in regulating the cell cycle by influencing cell division and survival.
Flow Cytometry: Flow cytometry is a powerful analytical technique used to measure the physical and chemical characteristics of cells or particles as they flow in a fluid stream through a beam of light, usually a laser. This method allows for the rapid analysis of thousands of cells per second, providing valuable information about cell size, granularity, and protein expression. In the context of cell cycle control, flow cytometry can be particularly useful for determining the distribution of cells across different phases of the cell cycle, helping researchers understand how cells regulate their growth and division.
G1 checkpoint: The G1 checkpoint is a critical control point in the cell cycle that occurs at the end of the G1 phase, where the cell assesses its environment and internal conditions to determine whether to proceed to DNA synthesis (S phase). This checkpoint ensures that the cell has adequate resources, proper growth signals, and that its DNA is undamaged before committing to replication. If conditions are not favorable, the cell can enter a resting state called G0 or initiate repair processes.
G1 phase: The G1 phase, or Gap 1 phase, is the first stage of interphase in the cell cycle, where the cell grows, carries out normal functions, and prepares for DNA replication. During this phase, the cell increases in size and synthesizes various proteins and organelles essential for DNA synthesis and subsequent cell division.
G2 checkpoint: The G2 checkpoint is a critical control mechanism in the cell cycle that occurs at the transition between the G2 phase and mitosis (M phase). This checkpoint ensures that DNA has been accurately replicated and that any damage to the DNA is repaired before the cell proceeds to divide. The G2 checkpoint plays a vital role in maintaining genomic integrity, preventing the propagation of damaged or incomplete genetic material.
G2 of Interphase: G2 of Interphase is the final sub-phase of Interphase where the cell undergoes rapid growth and prepares for mitosis. It involves the synthesis of proteins and organelles needed for cell division.
G2 phase: The G2 phase is the third subphase of interphase in the cell cycle, occurring after DNA replication and before mitosis. During this phase, the cell undergoes critical preparations for mitosis, including the synthesis of proteins and organelles required for cell division. The G2 phase ensures that the cell has accurately duplicated its DNA and has all the necessary components to successfully divide into two daughter cells.
G2/M checkpoint: The G2/M checkpoint is a crucial regulatory point in the cell cycle that occurs at the boundary between the G2 phase and the M phase, ensuring that cells are properly prepared to enter mitosis. This checkpoint assesses DNA integrity and the completion of DNA replication, allowing for repairs if necessary before proceeding. Proper function of this checkpoint is essential for maintaining genomic stability and preventing the proliferation of damaged cells.
Human growth hormone (HGH or hGH): Human Growth Hormone (HGH or hGH) is a peptide hormone produced by the pituitary gland that stimulates growth, cell reproduction, and cell regeneration. It plays a crucial role in regulating the growth and development of tissues and organs throughout the body.
Integrins: Integrins are transmembrane proteins that facilitate cell adhesion and communication by connecting the extracellular matrix to the cell's cytoskeleton. They play a crucial role in various cellular activities, including signaling pathways, migration, and maintaining tissue integrity. Integrins are essential for the structural and functional organization of tissues, linking cells together and allowing them to respond to changes in their environment.
Interphase: Interphase is the stage in the cell cycle where the cell prepares for division, encompassing the growth and DNA replication necessary for successful cell division. It is crucial for cellular function as it allows the cell to grow, replicate its DNA, and produce proteins needed for mitosis or meiosis.
M phase: The M phase, or mitotic phase, is the stage of the cell cycle where cell division occurs, resulting in two daughter cells. This phase encompasses both mitosis, which is the division of the nucleus, and cytokinesis, which is the division of the cytoplasm. The M phase is critical for growth, development, and tissue repair, and its proper regulation ensures genetic stability across generations of cells.
MAPK pathway: The MAPK (Mitogen-Activated Protein Kinase) pathway is a critical signaling cascade that transmits extracellular signals to the cell's nucleus, leading to various cellular responses, including growth, differentiation, and survival. This pathway plays a significant role in regulating the cell cycle and is also essential for processing genomic information in response to various stimuli.
Metaphase Checkpoint: The metaphase checkpoint is a critical regulatory point in the cell cycle, ensuring that all chromosomes are properly aligned and attached to the spindle apparatus before the cell proceeds to anaphase. This checkpoint prevents errors in chromosome segregation, which can lead to aneuploidy and other genetic abnormalities. The metaphase checkpoint is crucial for maintaining genomic stability during cell division.
Mitosis: Mitosis is the process of cell division that results in two genetically identical daughter cells, each containing the same number of chromosomes as the original cell. This process is essential for growth, development, and tissue repair in multicellular organisms, linking it to various biological concepts including cellular organization and reproduction.
P21: p21 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating the cell cycle, specifically functioning as a checkpoint that can halt the progression of cells through the cycle in response to DNA damage or stress signals. By inhibiting cyclin-CDK complexes, p21 helps maintain genomic stability and prevent the uncontrolled cell division that characterizes cancer. Its expression is often regulated by the tumor suppressor protein p53, linking it to both normal cellular function and cancer biology.
P27: p27 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating the cell cycle by inhibiting the activity of cyclin-CDK complexes, particularly in the transition from G1 to S phase. By controlling the progression of the cell cycle, p27 ensures that cells do not divide uncontrollably, linking its function to both normal cellular processes and cancer development.
P53: p53 is a crucial tumor suppressor protein that regulates the cell cycle and helps maintain genomic stability by preventing the proliferation of cells with damaged DNA. It plays a significant role in the control of cell growth, ensuring that cells do not divide uncontrollably, which is particularly important in the context of cancer development and gene regulation.
Proto-oncogenes: Proto-oncogenes are normal genes that play essential roles in cell growth, differentiation, and division. When mutated or abnormally expressed, these genes can become oncogenes, which contribute to the development of cancer by promoting uncontrolled cell proliferation. Understanding proto-oncogenes is crucial as they are key players in the regulation of the cell cycle and can influence cancer progression and gene regulation.
Ras: Ras is a family of small GTPase proteins that play a crucial role in transmitting signals within cells, particularly in the regulation of cell growth and differentiation. These proteins act as molecular switches that toggle between an active GTP-bound state and an inactive GDP-bound state, influencing key pathways involved in the cell cycle and cell signaling, making them integral to understanding processes like cell division and cancer development.
Rb protein: Rb protein, or retinoblastoma protein, is a crucial tumor suppressor that helps control the cell cycle by regulating the progression from the G1 phase to the S phase. By binding to and inhibiting transcription factors such as E2F, Rb protein plays a significant role in preventing uncontrolled cell division and thus acts as a barrier against cancer development.
Restriction Point: The restriction point is a critical checkpoint in the cell cycle, specifically at the G1 phase, where a cell decides whether to continue division or enter a resting state. This point assesses the cell's size, DNA integrity, and nutrient availability, ensuring that conditions are favorable for DNA synthesis and cell division. If conditions are not suitable, the cell may enter a quiescent state called G0, allowing it to avoid potential errors in replication.
Retinoblastoma protein (Rb): Retinoblastoma protein (Rb) is a tumor suppressor protein that plays a crucial role in regulating the cell cycle. It prevents excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide.
S phase: The S phase, or synthesis phase, is a key part of the cell cycle where DNA replication occurs, allowing a cell to double its genetic material before division. This phase is critical for ensuring that each daughter cell receives an identical set of chromosomes, maintaining genetic consistency and integrity across generations of cells.
Spindle assembly checkpoint: The spindle assembly checkpoint is a critical regulatory mechanism during cell division that ensures chromosomes are properly attached to the spindle apparatus before the cell proceeds to anaphase. This checkpoint helps prevent errors in chromosome segregation, which can lead to aneuploidy, a condition where cells have an abnormal number of chromosomes. By monitoring the attachment of spindle fibers to kinetochores, this checkpoint plays a vital role in maintaining genomic stability.
Tumor suppressor genes: Tumor suppressor genes are segments of DNA that regulate cell growth by inhibiting cell division and promoting apoptosis. They play a crucial role in preventing cancer development by maintaining genomic stability.
Tumor suppressor genes: Tumor suppressor genes are crucial segments of DNA that help regulate cell growth and division, preventing cells from growing uncontrollably. They produce proteins that function as checkpoints in the cell cycle, ensuring that damaged or abnormal cells do not proliferate, which is essential in maintaining normal cellular function and preventing cancer.
Ubiquitin ligase: Ubiquitin ligase is an enzyme that facilitates the attachment of ubiquitin, a small regulatory protein, to target proteins, marking them for degradation by the proteasome. This process is crucial for controlling protein levels within the cell and plays a significant role in regulating the cell cycle by targeting specific proteins for destruction at key points.