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GATE 2022 BT Q.43: solution and answer

GATE 2022 · BTQ.43 · 2 marks · MCQ

The enzymes involved in ubiquitinylation of cell-cycle proteins are

  1. (A)

    E₁ and E₂ only

  2. (B)

    E₁ and E₃ only

  3. (C)

    E₁ and E₄ only

  4. (D)

    E₁, E₂ and E₃

See the question in the paper
GATE 2022 BT question 43Tap to open full size

Answer and solution

ANSWER

The correct answer is (D) E₁, E₂ and E₃ — the ubiquitin-proteasome pathway that tags cell-cycle proteins for degradation universally requires this three-enzyme cascade (E1 activating, E2 conjugating, E3 ligating).

Official answer: DSource: Official answer key, GATE 2022 BT (IIT Kharagpur)

  1. Cell-cycle proteins destined for proteasomal degradation (e.g., cyclin B, securin, p27/CDK inhibitors) are tagged with polyubiquitin chains via a universal three-enzyme cascade: E1, E2 and E3.

  2. E1 (ubiquitin-activating enzyme) uses ATP to activate the C-terminal glycine of ubiquitin, forming a high-energy E1~ubiquitin thioester intermediate.

  3. E2 (ubiquitin-conjugating enzyme) accepts the activated ubiquitin from E1 by transthioesterification, forming an E2~ubiquitin intermediate — an obligatory carrier step that cannot be skipped.

  4. E3 (ubiquitin ligase — e.g., the APC/C or SCF complex acting on cell-cycle substrates) recognizes the specific substrate and mediates transfer of ubiquitin from E2 onto the substrate, building a polyubiquitin chain that the 26S proteasome recognizes.

  5. Option (A) E1 and E2 only is wrong: without E3 there is no substrate recognition, so ubiquitin is never delivered to the target protein.

  6. Option (B) E1 and E3 only is wrong: E2 is an obligatory intermediate between E1 and E3; the cascade cannot skip it.

  7. Option (C) E1 and E4 only is wrong: E4 is only a chain-elongation factor for a subset of substrates, not a universal component, and it does not substitute for E2 or E3.

  8. Option (D) E1, E2 and E3 is correct: these three enzymes acting in sequence form the minimal, universal cascade needed to ubiquitinate any cell-cycle protein for degradation.

KEY IDEA

Ubiquitin-mediated proteolysis of cell-cycle regulators (cyclins, securin, CDK inhibitors) by the proteasome always proceeds through the same enzymatic cascade: E1 (activation) → E2 (conjugation) → E3 (ligation, substrate specificity), so all three are required.

WATCH OUT FOR

Students often stop at "E1 activates, E3 ligates" and forget that E2 is an obligatory carrier intermediate between them (option B), or mistake E4 (a chain-elongation factor present only in some substrates) for a core, universal component (option C).

From the GATE 2022 BT paper. Every question of this paper · Download the full paper · All 7 Cell signalling questions, with notes

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