Cell Cycle Phases

To arrest the cell cycle to allow for DNA repair

Upregulation of pro-apoptotic genes

To halt cell cycle progression by phosphorylating Cdc25 phosphatases

Unregulated cell growth

Binding to Cyclin B and preventing import into the nucleus

Screening the genome for DNA damage and regulating the cell cycle accordingly

Phosphorylation of p53 and CHK1 and CHK2

Consolidating the cell cycle before progressing to M phase

To grow in size and synthesise mRNA and proteins required for DNA synthesis

A resting state where the cell is not actively trying to divide

To regulate the progression of the cell cycle through sequential increased expression

To detect DNA damage and promote repair mechanisms

P53

To detect DNA damage and promote repair mechanisms

The cell cycle is arrested and DNA repair mechanisms are promoted

A protein that works in tandem with P53 to serve as a quality assurance checkpoint

They are small and hydrophobic

A conformational change in the receptor leading to activation

To regulate the rate of gene expression

Ligand binding domain

Cellular response

To bind signalling molecules and induce a response

The actual need of the cell in response to the external stimulus

Signal transduction

To amplify the signal through a step-by-step process

To amplify the signal through a step-by-step process

To control the progression of the signal

To act as a secondary messenger molecule

To act as a secondary messenger molecule

To prevent over-activation of the signal

Signal amplification

To act as a secondary messenger molecule

Cellular response

Binding to host DNA

A highly variable amino terminal domain, a central conserved DNA binding domain, and a conserved carboxy-terminal ligand binding domain

4

Dissociation of a heat shock protein (HSP) from the nuclear receptor

In the cytosol or nucleus

Binding to the host DNA

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The primary function of the G1 phase is for the cell to grow in size, synthesise mRNA and proteins required for DNA synthesis. This phase is crucial for preparing the cell for DNA replication in the S phase.

Cyclins are proteins that regulate the cell cycle by controlling the progression from one phase to the next. They do this by binding to and activating CDKs (cyclin-dependent kinases), which then phosphorylate and activate other proteins involved in the cell cycle.

The G1/S checkpoint is a quality control mechanism that ensures the cell's genome is intact before allowing it to enter the S phase. If DNA damage is detected, the checkpoint arrests the cell cycle and activates DNA repair mechanisms.

p53 is a tumour suppressor protein that serves as a quality assurance checkpoint for cells wanting to progress from the G1 to S phase. It works in tandem with MDM2 and ATM to regulate the cell cycle and ensure genome integrity.

The G2/M checkpoint is a quality control mechanism that ensures the cell's DNA is properly replicated and ready for mitosis. It differs from the G1/S checkpoint in that it occurs after DNA replication and focuses on ensuring the accuracy of the genetic material.

ATM (Ataxia telangiectasia mutated) is a serine/threonine kinase that plays a central role in responding to DNA damage. It phosphorylates and activates p53, which then regulates the cell cycle and ensures genome integrity.

The G0 phase is a resting state where the cell is not actively trying to divide and is instead focused on maintaining normal cellular functions. The G1 phase, on the other hand, is a period of cell growth and preparation for DNA replication.

Cell cycle checkpoints are quality control mechanisms that ensure the cell cycle progresses only if certain conditions are met. They monitor for DNA damage, genetic integrity, and other factors to ensure the cell is prepared for the next phase of the cell cycle.

p53 ensures DNA integrity by phosphorylating CHK1 and 2, halting cell cycle progression. If DNA damage is not detected, it becomes the new 'template' for healthy DNA.

ATM/ATR screens the genome for single-strand breaks, leading to p53 phosphorylation, which promotes transcription of pro-apoptotic factors and cell cycle arrest.

14-3-3α binds to CDK/Cyclin B complex, preventing its import into the nucleus and mitosis.

The G2/M checkpoint arrests the cell cycle, allowing for DNA repair mechanisms to repair damage before progressing to mitosis.

p53 phosphorylation promotes transcription of pro-apoptotic factors and cell cycle arrest, ensuring genomic stability.

CHK1 and CHK2 phosphorylation halts cell cycle progression by phosphorylating Cdc25 phosphatases, preventing CDK1 activation.

p21 arrests the cell cycle, allowing for DNA repair mechanisms to repair damage before progressing to mitosis.

The G1/S checkpoint arrests the cell cycle, allowing for DNA repair mechanisms to repair damage before progressing to S phase. If DNA damage is not detected, it becomes the new 'template' for healthy DNA.

It allows them to move through the plasma membrane unimpeded.

Through conformational change within the receptor.

They are regions of receptors capable of forming temporary non-covalent bonds with signalling molecules.

The actual need of the cell.

Intracellular signal transduction.

Through tightly regulated transcriptional regulatory elements.

To bind signalling molecules and trigger signal transduction.

It triggers signal reception and transduction.

The primary mechanism is the number of steps involved in cell signalling, which provides multiple checkpoints. This is significant because it allows cells to control the activation of certain pathways and prevent over-activation.

The purpose is to amplify the signal, and the consequence is signal amplification.

Secondary messengers are vital components of some signalling pathways, and examples include Calcium, cAMP, cGMP, and Inositol triphosphate.

The purpose is to prevent over-activation of the signal, and the consequence of not doing so would be over-activation of the signal.

Phosphorylation is a post-translational modification that controls the progression of the signal, and its significance lies in the regulation of protein activity.

Proteins within the pathway are changed in some capacity, allowing them to transmit the signal. This transmission is significant because it ensures the signal reaches the response elements.

The step-by-step process allows for the signal to be amplified and regulated, and it relates to signal transduction by transmitting the signal from the receptor to the response elements.

Inositol triphosphate is a secondary messenger molecule that plays a crucial role in cell signalling, and it relates to other secondary messenger molecules by functioning in conjunction with them to transmit the signal.

This binding allows the signal to be transmitted to the response elements, ultimately leading to a cellular response.

Nuclear receptors directly regulate transcription by binding directly to host DNA, and are able to activate or repress gene expression.

Type 1 nuclear receptors have a highly variable amino terminal domain, a central conserved DNA binding domain, and a conserved carboxy-terminal ligand binding domain. Ligand binding in the cytosol results in the disassociation of heat shock proteins, which serves as the regulator of the nuclear receptor.

The final stage of cell signalling is the cellular response, where the signal reaches the response elements and leads to a response.

Ligand binding in the cytosol results in the disassociation of heat shock proteins, which serves as the regulator of the nuclear receptor, ultimately leading to the regulation of gene expression.

Nuclear receptors directly regulate transcription by binding directly to host DNA, and are able to activate or repress gene expression. They have a common structure, comprising of a highly variable amino terminal domain, a central conserved DNA binding domain, and a conserved carboxy-terminal ligand binding domain.

This binding allows the signal to be transmitted to the response elements, ultimately leading to a cellular response.

Ion Channel Linked Receptor

Conformational change in the receptor

Hydrophilic interaction

To orient the ligand correctly within the receptor

Intracellular Receptor

Dissociation constant (Kd)

To predict the binding of a ligand to a receptor

Enzyme Coupled Receptor

To form temporary non-covalent bonds with signalling molecules

Conformational change within receptors, activating its function

The actual need of the cell in response to external stimulus

Signal transduction

They are small and hydrophobic, able to move through the plasma membrane unimpeded

To initiate signal transduction pathways

To transduce signals from ligand binding to cellular responses

They are small and hydrophobic, able to move through the plasma membrane unimpeded

To phosphorylate the receptor

All of the above

To remove phosphates and deactivate the receptor

Ligand binding does not induce phosphorylation of the receptor

To anchor the receptor to the membrane

The permeability of the membrane to sodium ions increases

Recruitment of cell signaling intermediates

They are the most diverse group of receptors, involved in response to a wide variety of signals

To interact with cell signaling intermediates

Cellular response

They act as molecular switches

It anchors the receptor in the membrane

Activation of the G-protein

It is involved in signal transduction

They are distinct domains of the G-protein

Ion Channel linked receptors are involved in response to a narrow variety of signals, while G-protein coupled receptors are involved in response to a wide variety of signals

The receptor undergoes a conformational change, activating the protein channel

To facilitate downstream signaling via enzyme-linked activation of intermediate complexes

It hydrolyzes GTP, releasing a phosphate and returning to the resting state

Enzyme-coupled receptors

It moves to the receptor, inducing a conformational change

The receptor acts as an enzyme, catalyzing specific reactions

The alpha subunit releases a phosphate, returning to the resting state

To bind ligands, inducing a conformational change and activating the protein channel

They are small and hydrophobic

Conformational change within receptors activating its function

Ligand binding domain

The actual need of the cell in response to the external stimulus

Signal transduction

To transduce the signal to downstream effectors

Cellular response

To regulate gene expression

Receptor tyrosine kinases (RTKs)

Formation of RTK dimers

To remove phosphates and deactivate the receptor

Ligand binding leads to phosphorylation of the receptor in RTKs, but not in non-receptor tyrosine kinase receptors

Signal transduction

To recruit cell signalling intermediates

Ligand binding extracellular domain, single transmembrane alpha helix, and cytoplasmic tyrosine kinase domain

Activation of the tyrosine kinase domain

Enzyme coupled receptor

Polar interactions

Conformational change within the receptor

G-protein coupled receptor

Dissociation constant (Kd)

Intracellular receptors

Dissociation constant (Kd)

To predict the interaction points between the ligand and receptor

It releases Ca2+ into the cytosol

It activates protein kinase C (PKC)

It degrades phosphatidyl inositol (PTI) into DAG and IP3

It activates PPC, leading to IP3 and DAG production

It is activated by diacyl glycerol (DAG) and calcium ions

It releases Ca2+ into the cytosol

G-Protein Coupled Receptor

It is degraded by phospholipase C (PPC) into DAG and IP3

To activate the protein channel

It returns the receptor to its resting state

They act as enzymes themselves

To facilitate downstream signaling via enzyme-linked activation

RTKs are enzyme-coupled receptors, while non-RTKs are G-protein coupled receptors

To transmit signals from the receptor to downstream effectors

It returns the receptor to its resting state

They facilitate downstream signaling via enzyme-linked activation

Type I = Bind to ligands in the cytosol and then translocate to the nucleus Type II = Bind to ligands in the nucleus Type III = Bind to ligands in the cytosol and then translocate to the nucleus Type IV = Require an additional protein to bind to DNA

Endocrine Signalling = Signalling that occurs over long distances through the bloodstream Paracrine Signalling = Signalling that occurs between nearby cells Autocrine Signalling = Signalling that occurs within a single cell Juxtacrine Signalling = Signalling that occurs through direct cell-cell contact

DNA binding domain = Binds to specific DNA sequences Ligand binding domain = Binds to hormone molecules Dimerization domain = Allows receptors to form dimers Transactivation domain = Recruits coactivator proteins

Membrane bound ligands = Found on one cell and interact with membrane bound receptors on adjacent cells Communicating junctions = Allow for direct communication and transport of small molecules between cells Notch signalling = A highly conserved cell signalling pathway present in most eukaryotic cells Extracellular matrix glycoprotein = Interacts with membrane protein to facilitate signalling

Steroid receptors = Bind to steroids and interact with response elements Thyroid receptors = Bind to thyroid hormones and interact with response elements Retinoid receptors = Bind to vitamin A derivatives and interact with response elements Orphan receptors = Have no known ligand

Endocrine Signalling = Long-distance signalling through hormones Paracrine Signalling = Short-distance signalling between nearby cells Autocrine Signalling = Signalling within a single cell Juxtacrine Signalling = Direct cell-cell contact signalling

Gene activation = Results in changed cell function Transcriptional regulation = Regulates gene expression Ligand binding = Triggers receptor activation Dimerization = Allows receptors to bind to DNA

Membrane bound ligands = Direct interaction between cells through membrane bound proteins Communicating junctions = Direct cell-cell communication through gap junctions Notch signalling = Signalling pathway that regulates cell fate decisions Cell adhesion molecules = Mediate cell-cell adhesion and signalling

Type 1 = Ligand binding in the cytosol results in disassociation of a heat shock protein (HSP) Type 2 = Ligand binding in the nucleus results in activation of nuclear receptors Type 3 = Ligand binding in the cytosol results in activation of nuclear receptors Type 4 = Ligand binding in the nucleus results in disassociation of a heat shock protein (HSP)

Juxtacrine signalling = Signal is transmitted through direct cell-cell contact Endocrine Signalling = Signal is transmitted through the bloodstream to reach distant cells Paracrine Signalling = Signal is transmitted through the bloodstream to reach nearby cells Autocrine signalling = Signal is transmitted through the bloodstream to reach the same cell

Amino terminal domain = Highly variable region DNA binding domain = Conserved region that binds to host DNA Ligand binding domain = Conserved region that binds to ligand Carboxy-terminal domain = Region that regulates transcription

Type 1 = Regulation of gene transcription Type 2 = Regulation of cell growth Type 3 = Regulation of cell division Type 4 = Regulation of apoptosis

Cellular response = The final stage where the signal reaches the response elements Signal reception = The stage where the signal binds to the receptor Signal transduction = The stage where the signal is transmitted through the cytosol Signal integration = The stage where the signal is integrated with other signals

Type 1 = Ligand binding in the cytosol results in disassociation of a heat shock protein (HSP) Type 2 = Ligand binding in the nucleus results in activation of nuclear receptors Type 3 = Ligand binding in the cytosol results in activation of nuclear receptors Type 4 = Ligand binding in the nucleus results in disassociation of a heat shock protein (HSP)

Regulation of gene transcription = Directly regulate gene transcription by binding to host DNA Regulation of cell growth = Regulate cell growth by activating or inhibiting signaling pathways Regulation of cell division = Regulate cell division by controlling the cell cycle Regulation of apoptosis = Regulate cell death by activating or inhibiting signaling pathways

Juxtacrine signalling = Direct cell-cell contact Endocrine Signalling = Signal transmission through the bloodstream Paracrine Signalling = Signal transmission through the bloodstream to nearby cells Autocrine signalling = Signal transmission through the bloodstream to the same cell

Type 1 = Ligand binds in the cytosol, then translocates to the nucleus Type 2 = Ligand binds in the nucleus Type 3 = Heterodimers are formed with RXR Type 4 = Homodimers are formed with RXR

Endocrine Signalling = Signalling molecules are released into the bloodstream Paracrine Signalling = Signalling molecules are released into the surrounding tissue Juxtacrine Signalling = Signalling molecules are released directly into adjacent cells Autocrine Signalling = Signalling molecules act on the same cell that produced them

Ligand Binding Domain (LBD) = Forms temporary non-covalent bonds with signalling molecules DNA Binding Domain (DBD) = Binds to specific DNA sequences Dimerization Domain = Forms dimers with other nuclear receptors Transcriptional Activation Domain = Recruits transcriptional coactivators

Steroids = Small hydrophobic molecules that can diffuse through the plasma membrane Peptides = Large hydrophilic molecules that require a membrane receptor Amino Acids = Small hydrophilic molecules that can bind to membrane receptors Gases = Small molecules that can diffuse through the plasma membrane

Signal Reception = Ligand binding to receptor Signal Transduction = Intermediates are activated to transmit the signal Cellular Response = Final response to the signal is generated Signal Termination = Signal is terminated to prevent further response

Type 4 = Estrogen receptors Type 1 = Retinoic acid receptors Type 2 = Thyroid hormone receptors Type 3 = Vitamin D receptors

Endocrine Signalling = Insulin regulating blood sugar levels Paracrine Signalling = Histamine released during allergic reactions Juxtacrine Signalling = Notch signalling during cell-cell contact Autocrine Signalling = Platelet-derived growth factor (PDGF)

Ligand = Binds to receptor to initiate signalling Receptor = Binds to ligand to initiate signalling Signal Transduction Pathway = Transmits signal from receptor to response elements Response Elements = Binds to transcription factors to regulate gene expression

Type I = Bind to ligands in the cytosol and then translocate to the nucleus Type II = Bind to ligands in the nucleus Type III = Require heterodimerization with RXR for activity Type IV = Bind to ligands in the cytosol and then translocate to the nucleus as homodimers

Juxtacrine = Signal transmission through direct cell-cell contact Endocrine = Hormone signaling over long distances Paracrine = Local signaling between nearby cells Autocrine = Self-stimulation of cell signaling

Estrogen receptor = Estrogen Thyroid receptor = Thyroid hormone Retinoic acid receptor = Retinoic acid Glucocorticoid receptor = Glucocorticoids

Cyclic AMP = Secondary messenger in cell signaling Inositol triphosphate = Releases calcium from the endoplasmic reticulum Diacyl glycerol = Activates protein kinase C Calcium = Involved in protein kinase C activation

Autocrine = Cell surface receptors Paracrine = Cell surface receptors Endocrine = Intracellular receptors Juxtacrine = Cell surface receptors

Estrogen receptor = DNA binding domain Thyroid receptor = Ligand binding domain Retinoic acid receptor = DNA binding domain Glucocorticoid receptor = Ligand binding domain

G-protein coupled receptor = Signal transduction through G-proteins Receptor tyrosine kinase = Signal transduction through phosphorylation Nuclear receptor = Gene regulation through transcription Cytokine receptor = Signal transduction through JAK/STAT pathway

p53 = Regulation of cell growth and DNA repair Cyclin = Regulation of cell cycle progression CHK1 = Regulation of cell cycle checkpoints ATM = Detection of DNA damage

Endocrine Signalling = Signaling molecules act on distant cells Paracrine Signalling = Signaling molecules act on nearby cells Autocrine Signalling = Signaling molecules act on the same cell Juxtacrine Signalling = Signaling molecules act on adjacent cells

Type I Nuclear Receptors = Bind to ligands in the cytosol and then translocate to the nucleus Type II Nuclear Receptors = Already in the nucleus, bound to DNA, waiting for ligand Type III Nuclear Receptors = Bind to ligands in the nucleus Type IV Nuclear Receptors = Bind to ligands in the cytosol and then translocate to the nucleus with the help of chaperone proteins

Hormones = Endocrine Signalling Cytokines = Paracrine Signalling Growth Factors = Autocrine Signalling Neurotransmitters = Juxtacrine Signalling

Form heterodimers with RXR = Type II Nuclear Receptors Bind to ligands in the cytosol = Type I Nuclear Receptors Already in the nucleus, bound to DNA = Type II Nuclear Receptors Bind to ligands in the nucleus = Type III Nuclear Receptors

Endocrine Signalling = Insulin signaling from pancreas to liver Paracrine Signalling = Signaling between neurons in the brain Autocrine Signalling = Platelet-derived growth factor signaling Juxtacrine Signalling = Signaling between adjacent endothelial cells

Hormones = Endocrine Signalling Growth Factors = Autocrine Signalling Cytokines = Paracrine Signalling Neurotransmitters = Juxtacrine Signalling

Bind to DNA as monomers = Type I Nuclear Receptors Bind to DNA as heterodimers = Type II Nuclear Receptors Bind to DNA as homodimers = Type III Nuclear Receptors Bind to DNA as monomers, homodimers or heterodimers = Type IV Nuclear Receptors