Protein degradation: ubiquitin-proteasome system: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Protein degradation: ubiquitin-proteasome system

Sample item

A patient with multiple myeloma is treated with bortezomib. Which mechanism underlies its action?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

C. Inhibition of the 26S proteasome, so ubiquitin-tagged proteins accumulate and plasma cells undergo apoptosis

Proteins destined for destruction are tagged with chains of ubiquitin (usually linked through lysine 48) and degraded by the 26S proteasome in an ATP-dependent step. Plasma cells make huge amounts of immunoglobulin and depend on proteasomal clearance of misfolded protein, and proteasome inhibition also stabilises IkB and blocks NF-kB. Peripheral neuropathy is a characteristic adverse effect.

Option by option

  • A. Inhibition of the mTOR kinase

    mTOR inhibition is the action of sirolimus and everolimus.

  • B. Inhibition of topoisomerase II

    Topoisomerase II inhibition is the action of etoposide and anthracyclines.

  • C. Inhibition of the 26S proteasome, so ubiquitin-tagged proteins accumulate and plasma cells undergo apoptosis (correct)

    Proteasome inhibition causes build-up of misfolded proteins and suppresses NF-kB survival signalling in myeloma cells.

  • D. Inhibition of histone deacetylase

    HDAC inhibition is the action of vorinostat.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is C, Inhibition of the 26S proteasome, so ubiquitin-tagged proteins accumulate and plasma cells undergo apoptosis. Proteins destined for destruction are tagged with chains of ubiquitin (usually linked through lysine 48) and degraded by the 26S proteasome in an ATP-dependent step.

Why is "Inhibition of the mTOR kinase" not the answer?

mTOR inhibition is the action of sirolimus and everolimus.

Why is "Inhibition of topoisomerase II" not the answer?

Topoisomerase II inhibition is the action of etoposide and anthracyclines.

Why is "Inhibition of histone deacetylase" not the answer?

HDAC inhibition is the action of vorinostat.

What concept does this question test?

It tests Protein degradation: ubiquitin-proteasome system in Biochemistry. Plasma cells make huge amounts of immunoglobulin and depend on proteasomal clearance of misfolded protein, and proteasome inhibition also stabilises IkB and blocks NF-kB. Peripheral neuropathy is a characteristic adverse effect.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Protein degradation: ubiquitin-proteasome system?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.