The table below lists cell cycle regulatory proteins and their known functionsCell Cycle regu latory proteins Function A Cdk-activating kinase (CAK) (i) Suppresses G1/S-Cdk and S-Cdk activation in G1; helps cells withdraw from cell cycle when they terminally differentiate; phosphorylation by Cdk2 triggers its ubiquitylation by SCF. B Wee1 kinase (ii) Suppresses G1/S-Cdk and S-Cdk activities following DNA damage C p27 (mammals) (iii) Phosphorylates inhibitory sites in Cdks: primarily involved in suppressing Cdk1 activity before mitosis D p21 (mammals) (iv) Phosphorylates an activating site in Cdks
The cell cycle is tightly controlled by a complex network of proteins, including cyclin-dependent kinases (Cdks) and their regulators. These regulatory proteins ensure that the cell cycle progresses in an orderly manner, preventing errors such as incomplete DNA replication or improper chromosome segregation. The table provided lists several key cell cycle regulatory proteins and their corresponding functions. We need to match the proteins with their correct functions based on the known roles in cell cycle control.
| Cell Cycle regulatory proteins | Function |
|---|---|
| A. Cdk-activating kinase (CAK) | (i) Suppresses G1/S-Cdk and S-Cdk activation in G1; helps cells withdraw from cell cycle when they terminally differentiate; phosphorylation by Cdk2 triggers its ubiquitylation by SCF. |
| B. Wee1 kinase | (ii) Suppresses G1/S-Cdk and S-Cdk activities following DNA damage |
| C. p27 (mammals) | (iii) Phosphorylates inhibitory sites in Cdks: primarily involved in suppressing Cdk1 activity before mitosis |
| D. p21 (mammals) | (iv) Phosphorylates an activating site in Cdks |
Let's examine the functions of each protein based on the correct matching:
The function assigned to CAK is (iv) "Phosphorylates an activating site in Cdks". This is correct. CAK, composed of Cdk7, cyclin H, and MAT1, phosphorylates the threonine residue in the T-loop of Cdks. This phosphorylation is essential for the full activation of Cdk-cyclin complexes, such as those driving the G1/S, S, and M phases of the cell cycle.
Wee1 kinase is matched with function (iii) "Phosphorylates inhibitory sites in Cdks: primarily involved in suppressing Cdk1 activity before mitosis". This is also correct. Wee1 is a kinase that phosphorylates the tyrosine and threonine residues (specifically Tyr15 and sometimes Thr14) near the ATP-binding site of Cdks, particularly Cdk1. This inhibitory phosphorylation prevents Cdk activity and helps control the timing of cell cycle transitions, especially entry into mitosis.
p27 is a Cdk inhibitor protein (CKI) in mammals. It is matched with function (i) "Suppresses G1/S-Cdk and S-Cdk activation in G1; helps cells withdraw from cell cycle when they terminally differentiate; phosphorylation by Cdk2 triggers its ubiquitylation by SCF". This description accurately reflects the role of p27. It binds to and inhibits G1/S-Cdks (like Cdk2-cyclin E) and S-Cdks (like Cdk2-cyclin A), controlling progression through the G1 phase and preventing premature entry into the S phase. High levels of p27 are associated with cells exiting the cell cycle and differentiating. Phosphorylation by Cdk2 indeed marks p27 for degradation by the SCF ubiquitin ligase complex, allowing cell cycle progression.
p21 is another mammalian CKI, often induced by the p53 tumor suppressor protein in response to DNA damage. It is matched with function (ii) "Suppresses G1/S-Cdk and S-Cdk activities following DNA damage". This is correct. Following DNA damage, p53 is activated and stimulates the expression of p21. p21 then binds to and inhibits Cdk-cyclin complexes, including G1/S-Cdks and S-Cdks. This inhibition causes cell cycle arrest, typically in G1 or S phase, allowing time for DNA repair before replication or division proceeds.
Based on the known functions of these cell cycle regulatory proteins, the correct match is:
This matches the first option provided.
During cell cycle, entry in the S-phase is tightly regulated. This is possible because:
A. APC/C promotes ubiquitination of S-phase cyclins and mitotic cyclins, marking them for proteolyses at the mitotic exit.
B. Cyclin B1 helps in the activation of S-phase CDKs only in late G1.
C. As mitotic CDK activity declines in late mitosis, cdc14 phosphatase activates APC/C by dephosphorylating Cdh1, thus promoting formation of APC/CCdh1
D. Securin keeps S-phase cyclins in inactive state till late G1.
Which one of the options represents all correct statements?
Following statements were made about cell cycle regulation:
A. De novo synthesis and destruction of Cyclin B are essential for cell cycle progression in yeast.
B. De novo synthesis and destruction of Cyclin B and the related Cyclin dependent Kinase (CDK) are essential for cell cycle progression.
C. CDK activity is regulated by both activating and inhibitory phosphorylation.
D. Retinoblastoma (Rb) functions as an inhibitor of G2 to M transition.
E. Inactivation of Sic 1 is essential for transition into S phase.
Which one of the following represents the combination of the correct statements?
Following statements were made about the characteristics of cyclin proteins:
A. Synthesis of M-cyclin is dependent on the cyclin mRNA that is newly transcribed after every cycle.
B. Destruction of M-cyclin toward the end of mitosis is driven by ubiquitin independent proteolytic system.
C. G1 cyclins can be activated by mitogenic factors.
D. Retinoblastoma (Rb) is a key target of the activated cyclin D - Cdk 4/6 complex.
E. While cyclin A1 expression is ubiquitous, cyclin A2 expression is restricted to the germ cell lineages.
Which one of the following options contains a combination of all correct statements?
To test the impact of cAMP on protein kinase A conformation in cells, an investigator made FRET biosensor by fusing two fluorescent proteins at the N-and C-terminus of protein kinase A. In the absence of cAMP in the cellular milieu, no FRET signal was detected. However, upon cAMP addition, a strong emission at 530 nm was observed. What could be the best configuration of fluorophores that were used by the investigator?
Given below are a few steps in clathrin‐coated vesicle formation in the secretory pathway.
(A) Receptor‐ligand recognition and binding
(B) Recruitment of adapter protein and clathrin
(C) Vesicle formation
(D) Uncoating of clathrin coats
Choose the option that correctly identifies the sequence of events in making a clathrin‐coated vesicle.