Question

The enzymes involved in ubiquitinylation of cell-cycle proteins are

• A. E$_1$ and E$_2$ only
• B. E$_1$ and E$_3$ only
• C. E$_1$ and E$_4$ only
• D. E$_1$, E$_2$ and E$_3$

Hint:

Think “1-2-3”: E$_1$ activates ubiquitin, E$_2$ carries (conjugates) it, and E$_3$ ligates it to the target protein, giving substrate specificity.

Answer 1

The Correct Option is D

Ubiquitinylation (or ubiquitination) is a three-enzyme cascade that tags proteins, including cell-cycle regulators, for degradation via the proteasome.
Step 1: Role of E$_1$ – Ubiquitin-activating enzyme.
E$_1$ activates ubiquitin in an ATP-dependent reaction.
Ubiquitin is first adenylated and then forms a high-energy thioester bond with a cysteine residue on E$_1$.
This step “charges” ubiquitin so it can be transferred further in the pathway.
Step 2: Role of E$_2$ – Ubiquitin-conjugating enzyme.
Activated ubiquitin is then transferred from E$_1$ to a cysteine residue on E$_2$.
E$_2$ carries ubiquitin and interacts with specific E$_3$ ligases.
Step 3: Role of E$_3$ – Ubiquitin ligase.
E$_3$ recognizes the target protein (substrate) and brings it together with the E$_2$–ubiquitin complex.
It catalyzes the transfer of ubiquitin from E$_2$ to a lysine residue on the substrate protein.
Because E$_3$ binds the substrate, it provides specificity to ubiquitinylation of particular cell-cycle proteins.
Step 4: Conclusion.
All three enzymes—E$_1$ (activating), E$_2$ (conjugating), and E$_3$ (ligase)—are essential components of the ubiquitinylation cascade.
There is no standard “E$_4$” enzyme in this pathway.
Therefore, the correct choice is (D) E$_1$, E$_2$ and E$_3$.