Question

Cyclin-dependent kinases (Cdks) A. occur only in the M phase. B. are always inactivated by phosphorylation. C. typically phosphorylate proteins on tyrosine residues. D. in addition to binding cyclin, require other modifications for activity. E. that phosphorylate \(\mathrm{Rb}\) (retinoblastoma sensitivity) protein inhibit the synthesis of S-phase proteins.

Short answer

D. In addition to binding cyclin, they require other modifications for activity.

Step-by-step solution

Option A: Occur only in M phase

Although Cdks are important during the M phase, they are also active during other phases of the cell cycle, such as S phase and G2 phase. So option A is incorrect.

Option B: Always inactivated by phosphorylation

Phosphorylation is a common way to regulate the activity of Cdks, but in some cases, they can also be activated by phosphorylation. Therefore, option B is incorrect.

Option C: Typically phosphorylate proteins on tyrosine residues

Cdks generally phosphorylate their target proteins on serine or threonine residues and not on tyrosine residues. Therefore, option C is incorrect.

Option D: In addition to binding cyclin, require other modifications for activity

To be active, Cdks bind to their corresponding cyclins, which is a necessary component. Additionally, they often require phosphorylation or dephosphorylation modifications to regulate their activity. Thus, option D is the correct statement.

Option E: Phosphorylate retinoblastoma (Rb) protein to inhibit the synthesis of S-phase proteins

Cdks that phosphorylate Rb protein actually promote the synthesis of S-phase proteins. Rb protein, when not phosphorylated, binds with E2F transcription factors, suppressing the transcription of S-phase genes. When Cdks phosphorylate Rb, it releases E2F, allowing the transcription of S-phase genes to proceed. Therefore, option E is incorrect. In conclusion, the correct statement about Cyclin-dependent kinases (Cdks) is: D. In addition to binding cyclin, they require other modifications for activity.

Key concepts

Cell Cycle Regulation

The cell cycle comprises a series of well-orchestrated events that lead to cell division. Cyclin-dependent kinases (Cdks) are essential enzymes that drive this cell cycle by catalyzing the phosphorylation of target proteins. These kinases are not confined to any single phase; they play pivotal roles during various stages, such as the G1, S, and G2 phases, as well as during mitosis or the M phase.

Cdks are regulated by several mechanisms. One primary way is through their interaction with cyclins, proteins whose levels fluctuate throughout the cell cycle. Binding to cyclins is necessary for Cdks to become active, but that's not the whole story. Other modifications, like phosphorylation at specific residues, can either enhance or inhibit Cdk activity. This nuanced control ensures that cells only move to the next phase when they are ready, preventing errors that could lead to cell death or uncontrolled cell division, which is a hallmark of cancer.

Protein Phosphorylation

Protein phosphorylation is a crucial post-translational modification involving the addition of a phosphate group, typically to serine, threonine, or tyrosine residues of proteins. This process is catalyzed by enzymes known as kinases, with Cdks being a key group. By adding this phosphate group, the shape and function of the protein target can drastically change.

In the context of the cell cycle, phosphorylation can switch 'on' or 'off' the activity of proteins, essentially acting as traffic signals that dictate the cell's progression through its cycle. Contrary to some misconceptions, phosphorylation doesn't always inhibit enzymes like Cdks; it can also activate them, depending on the residues being phosphorylated and the context within the cell. This underscores a complex regulatory network where the precise timing and location of phosphorylation are critical.

Rb Protein

The retinoblastoma protein, or Rb, is a pivotal tumor suppressor involved in cell cycle control. Its activity is regulated by phosphorylation, with Cdks playing a central role in this process. When Rb is unphosphorylated, it binds to E2F transcription factors, effectively putting the brakes on the cell cycle and preventing progression to the DNA synthesis phase (S phase).

However, when Cdks phosphorylate Rb, this changes. The phosphorylated Rb releases E2F, which then activates the transcription of genes necessary for DNA replication and the subsequent S phase of the cell cycle. It's this delicate balance of phosphorylation and dephosphorylation that governs the cell's progression through the cycle and ensures genomic integrity, thwarting potential pathways to cancer development when functioning properly.

Cyclin Interactions

Cdks require partnering with a group of regulatory proteins known as cyclins to become fully active. Cyclins are produced and degraded in a cyclical pattern, corresponding with the different stages of the cell cycle, ensuring that the right Cdks are active at the appropriate times.

These interactions are highly specific; different cyclins bind to specific Cdks, directing them to particular substrates, and therefore, precise cell cycle stages. This specificity is vital - without the right cyclin-Cdk complexes at the right time, the cell cycle could be derailed, leading to cell death or uncontrolled proliferation. The requirement for cyclin binding, along with additional modifications mentioned earlier, adds layers of control that safeguard the fidelity of cell division.