Retta - L12

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Questions and Answers

What is the main role of ubiquitination in the context of protein stability?

It modulates the stability and degradation of proteins. (correct)

It prevents the synthesis of proteins altogether.

It permanently stabilizes proteins within the cell.

It enhances the activity of all regulatory proteins.

Which component plays a crucial role in the cyclical nature of protein degradation during the cell cycle?

Cyclin-dependent kinase (Cdk)

Ubiquitin ligase (E3)

Proteasome complex

Ubiquitin (correct)

What is the typical lifetime of regulatory proteins involved in the cell cycle?

They persist until the cell undergoes division.

They last for several days in the cell.

They are produced and degraded within minutes to hours. (correct)

They are inactive after synthesis and require activation.

What action does the enzyme ubiquitin ligase (E3) perform?

It links ubiquitin to target proteins. Signup and view all the answers

Why is cyclical proteolysis considered a regulated process?

It allows for timely removal of proteins as per cellular requirements. Signup and view all the answers

What is the primary function of cyclins in the cell cycle?

To regulate the progression of the cell cycle through degradation. Signup and view all the answers

What is the primary function of the ubiquitin-proteasome system?

To degrade non-functional or abnormal proteins Signup and view all the answers

Which enzyme is responsible for the initial activation of ubiquitin in the ubiquitin-proteasome system?

Ubiquitin activating enzyme (E1) Signup and view all the answers

What modification must a target protein undergo for the SCF ubiquitin ligase to recognize it for ubiquitination?

Phosphorylation Signup and view all the answers

What defines the APC/C's activation compared to the SCF complex during the cell cycle?

APC/C is activated by accessory proteins at specific times. Signup and view all the answers

Which of the following enzymes does NOT play a role in the ubiquitination process?

E4 - Ubiquitin releasing enzyme Signup and view all the answers

In what context does polyubiquitylation occur?

It occurs when multiple ubiquitins attach to one amino acid residue. Signup and view all the answers

What role do small peptides and amino acids play after proteasomal degradation of polyubiquitylated proteins?

They are reused by the cell for synthesizing new proteins. Signup and view all the answers

What is the role of Cdh1 in the cell cycle?

It interacts with the APC/C to activate it during G1. Signup and view all the answers

Which protein is necessary for the activation of APC/C in M phase?

Cdc20 Signup and view all the answers

What process does activated APC/C primarily regulate?

Ubiquitylation of proteins for degradation. Signup and view all the answers

What is the purpose of CKIs in the cell cycle?

To inhibit the cyclin-CDK complex. Signup and view all the answers

What must occur before a CKI can be ubiquitinated?

It must be phosphorylated by a kinase. Signup and view all the answers

What is the significance of growth factors in the cell cycle?

They promote the transcription of cyclin genes. Signup and view all the answers

How does an integrin contribute to cell proliferation?

By mediating signal transduction with growth factors. Signup and view all the answers

What is the role of the proteasome in the cell cycle?

To degrade ubiquitinated target proteins. Signup and view all the answers

What occurs when M-cyclin is degraded?

The cyclin-Cdk complex becomes inactive. Signup and view all the answers

What is the primary function of Rb (retinoblastoma protein) when it is not phosphorylated?

It inhibits the transcription factor E2F. Signup and view all the answers

What triggers the cyclin-Cdk complex to promote cell cycle progression?

The phosphorylation of the Rb protein. Signup and view all the answers

Which condition can prevent the cyclin-Cdk complex from functioning even if it is present?

Presence of CKIs (cyclin-dependent kinase inhibitors). Signup and view all the answers

How do mutations in genes encoding for CKIs affect the cell cycle in the presence of DNA damage?

They lead to a loss of CKI function, allowing cell cycle progression. Signup and view all the answers

What role do reactive oxygen species (ROS) play in the context of cell cycle control?

They mediate signal transduction in physiological levels. Signup and view all the answers

What occurs when there is excessive production of reactive oxygen species?

It induces oxidative stress and potential DNA damage. Signup and view all the answers

Which of the following is true regarding the activation of the cyclin-Cdk complex?

It depends on successful phosphorylation of target proteins. Signup and view all the answers

What must occur in order to remove CKIs and allow the cell cycle to resume?

Proteolysis of the CKIs. Signup and view all the answers

What consequence does the malfunction of Rb phosphorylation have on the cell cycle?

It circumvents cell cycle checkpoints. Signup and view all the answers

Which signaling factors must be present in the environment for the cell cycle to be correctly regulated?

Growth factors and intact DNA. Signup and view all the answers

What role does Cdc25 phosphatase play in the cell cycle?

It removes inhibitory phosphorylation from Cdk1. Signup and view all the answers

Which of the following is most directly responsible for blocking the G1/S-Cdk and S-Cdk complexes?

Cdk inhibitory proteins like p21 Signup and view all the answers

What happens to terminally differentiated cells regarding the cell cycle?

They are blocked from proceeding due to CKIs like p27. Signup and view all the answers

What is the primary function of the S-Cdk complex during the S-phase?

To initiate DNA replication and block re-replication. Signup and view all the answers

Which of the following statements accurately describes the role of the ORC complex?

It binds to replication origins and recruits additional proteins. Signup and view all the answers

How is the S-phase prevented from occurring more than once per cell cycle?

Via phosphorylation of the ORC complex by S-Cdk. Signup and view all the answers

Which proteins are considered to have reverse effects on the Cdk activity before mitosis?

Wee1 and CKIs like p16 Signup and view all the answers

What is the role of SCF in the cell cycle control?

To degrade inhibitory proteins for cell cycle progression. Signup and view all the answers

Study Notes

Cell Cycle Control System

The cell cycle is regulated by cyclical proteolysis, with ubiquitin as a key target for degradation.
Cyclins are proteins involved in the progression of the cell cycle, sensitive to ubiquitination and time-limited in function.
Ubiquitination allows for the modulation of protein stability, facilitating rapid degradation after their functional period.

Ubiquitin-Proteasome System (UPS)

The UPS mediates cyclical proteolysis, utilizing a small regulatory protein called ubiquitin (76 amino acids, 8.6 kDa).
Ubiquitin is attached to target proteins through a process involving three main enzymes: E1 (activating enzyme), E2 (conjugating enzyme), and E3 (ligating enzyme).
Polyubiquitylation refers to the addition of multiple ubiquitins to a protein, marking it for degradation by the proteasome.

Ubiquitin Ligases in Cell Cycle Regulation

Two primary ubiquitin ligases active in the cell cycle are SCF (Skp1-Cullin-F-box protein) and APC/C (Anaphase-Promoting Complex/Cyclosome).

SCF Complex

The SCF complex is continuously active and mediates protein degradation during the G1/S phase.
Target proteins need to be phosphorylated to be recognized by SCF for ubiquitination and degradation.
SCF triggers proteolysis of G1/S cyclins and Cyclin-CDK inhibitors (CKIs) such as p21 and p53.

APC/C Complex

The APC/C complex promotes the metaphase-anaphase transition and is not constitutively active; it requires activation by accessory proteins (Cdh1 in G1, Cdc20 in M phase).
Once activated, APC/C initiates the ubiquitination of target proteins, including M-cyclin, leading to their degradation.

Proteolysis and Cell Cycle Transition

Regulated proteolysis by APC/C is crucial for transitioning from metaphase to anaphase during mitosis.
The degradation of proteins at specific intervals ensures proper cell cycle progression.

Transcriptional Regulation

Cell cycle control also depends on transcriptional activities triggered by growth factors, which stimulate the transcription of cyclin genes.
Cyclin D1 synthesis is induced by growth factors and is essential for the formation of the cyclin-Cdk complex, necessary for cell cycle entry.

Role of Rb Protein

The retinoblastoma protein (Rb) inhibits transcription factors required for S-phase entry when not phosphorylated.
Cyclin-Cdk complexes phosphorylate Rb, allowing the transcription factor E2F to initiate transcription of S-phase-promoting genes.

CKIs and DNA Damage Response

CKIs (like p21) can block the cyclin-Cdk complex, inhibiting cell cycle progression.
DNA damage activates the production of CKIs, which prevent cell cycle advancement until the damage is repaired.
CKIs are themselves regulated by ubiquitination; their inability to be degraded can lead to uncontrolled cell cycle progression.

Sensitivity to Redox Signaling

The cell cycle control system is influenced by redox signaling mediated by reactive oxygen species, which can act as signaling molecules produced by mitochondria.
Proper levels of reactive oxygen species are essential for physiological signal transduction, affecting overall cell cycle regulation.### Cellular Dysfunction and Oxidative Stress
Abnormal cellular processes can lead to oxidative stress, damaging proteins and DNA.
Reactive oxygen species (ROS) mediate DNA damage through abnormal oxidation.
High ROS levels can disrupt cell cycle regulation mechanisms.

Regulation of Cell Cycle

Growth factors trigger the activation of the cell cycle through specific receptors and signaling pathways.
Cdc25 phosphatase activates M cyclin-Cdk necessary for entering M phase; its function is sensitive to oxidation.
Cyclin-dependent kinase inhibitors (CKIs) like p21 and p16 block cell cycle progression, especially in terminally differentiated cells.

CKIs and Cell Cycle Regulation

CKIs are vital for phosphorylating and activating Cdks involved in the cell cycle.
Wee1 kinase inhibits Cdk1 activity pre-mitosis whereas Cdc25 removes inhibitory phosphorylation, allowing progression.
p27 is an inhibitor that blocks terminally differentiated cells from re-entering the cell cycle.

S-Phase and DNA Replication

S-Cdk complex plays a pivotal role in initiating DNA replication, preventing re-replication.
ORC (origin recognition complex) and Cdc6 are critical in forming pre-replicative complexes at replication origins.
G1 phase cells can initiate DNA replication; G2 cells cannot, as they have already replicated DNA.

Chromosome Duplication

Histones and other chromosomal components must be replicated during the S-phase.
Cohesin complex holds sister chromatids together until anaphase, aiding in chromosomal stability.

Mitosis and M-Phase

M-Cdk drives mitotic entry; condensins compact chromosomes in preparation for segregation.
Mitosis is divided into prophase, prometaphase, metaphase, anaphase, and telophase, each with distinct cellular changes.
Proteolysis of cohesin during anaphase is essential for sister chromatid separation.

Phases of Mitosis

Prophase: Chromosomes condense and the mitotic spindle begins to form.
Prometaphase: Nuclear envelope disassembles, allowing spindle attachment to kinetochores.
Metaphase: Chromosomes align at the spindle equator, attached to opposite poles.
Anaphase: Sister chromatids separate and are moved to opposite poles by shortening microtubules.
Telophase: Nuclear envelope re-forms around chromosomes, which decondense.

Cytokinesis

Cytokinesis follows mitosis, separating the cytoplasm and completing the cell division process.
The contractile ring formed by actomyosin is crucial for the division of the cytoplasm.

Important Concepts

Semi-conservative replication of DNA and centrosomes occurs during S-phase.
Cell cycle checkpoints prevent progression under unfavorable conditions, ensuring DNA damage is repaired before replication continues.

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Description

This quiz explores the mechanisms regulating the cell cycle, focusing on the role of ubiquitin and the ubiquitin-proteasome system. Understand the function of cyclins, the enzymatic process of ubiquitination, and the involvement of key ubiquitin ligases in cell cycle progression.