Affinage

MZT2B

Mitotic-spindle organizing protein 2B · UniProt Q6NZ67

Length
158 aa
Mass
16.2 kDa
Annotated
2026-06-10
3 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: UniProt preferred faithfulness: 1/1 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MZT2B is a γ-tubulin ring complex (γ-TuRC) component implicated in centrosome and mitotic spindle assembly, identified through synthetic lethality with FBXO42 loss alongside the related γ-TuRC protein MZT1 [PMID:bio_10.1101_2025.04.22.649889]. Beyond this spindle-organizing role, MZT2B supports mitochondrial function in non-small-cell lung cancer cells: its depletion reduces oxygen consumption, ATP production, mitochondrial membrane potential, and disrupts redox homeostasis, with downregulation of the cytochrome c oxidase subunit COX5B; re-expression of COX5B or glucose supplementation rescues the anti-proliferative effect, placing COX5B downstream of MZT2B in sustaining oxidative phosphorylation and tumor cell proliferation (PMID:41213905). Beyond these findings, no structural mechanism or direct biochemical characterization of MZT2B has been established in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2025 Medium

    Whether MZT2B has a functional role beyond a presumed structural one was unknown; loss-of-function in cancer cells revealed it sustains mitochondrial oxidative phosphorylation via COX5B.

    Evidence shRNA/CRISPR knockout in NSCLC lines with respiration assays, redox measurements, COX5B/glucose rescue, and xenografts

    PMID:41213905

    Open questions at the time
    • mechanism by which MZT2B controls COX5B expression is not defined
    • no structural or in vitro reconstitution of MZT2B
    • link between the spindle role and mitochondrial role unresolved
  2. 2025 Low

    The pathway context of MZT2B was uncharacterized; a genome-wide screen placed it in centrosome/spindle assembly through synthetic lethality with FBXO42 alongside MZT1.

    Evidence genome-wide CRISPR knockout synthetic-lethality screen (preprint)

    PMID:bio_10.1101_2025.04.22.649889

    Open questions at the time
    • single screen result, not independently confirmed
    • no direct biochemical demonstration of MZT2B in γ-TuRC in this study
    • mechanism of FBXO42 dependence unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MZT2B mechanistically connects its γ-TuRC/spindle association to control of COX5B and mitochondrial respiration remains unresolved.
  • no structural model of MZT2B
  • no direct molecular activity assigned
  • mechanism coupling spindle function and mitochondrial regulation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Partners
MZT1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 MZT2B knockdown or CRISPR/Cas9 knockout in NSCLC cells impaired mitochondrial respiration, reducing oxygen consumption rates, ATP production, mitochondrial membrane potential, and cellular redox homeostasis (ROS, GSH/GSSG ratio), and downregulated COX5B (cytochrome c oxidase subunit 5B) expression; restoring COX5B or increasing glucose concentration rescued the anti-proliferative effects of MZT2B depletion, placing COX5B downstream of MZT2B in mitochondrial function regulation. shRNA knockdown and CRISPR/Cas9 knockout in NSCLC cell lines; mitochondrial respiration assays (OCR, ATP, membrane potential, ROS); rescue experiments with COX5B overexpression and glucose supplementation; subcutaneous xenograft mouse models Cell death & disease Medium 41213905
2025 Genome-wide CRISPR knockout screen identified synthetic lethality between FBXO42 mutation and mutations in γ-tubulin ring complex proteins MZT1 and MZT2B, indicating that MZT2B functions in centrosome and/or mitotic spindle assembly and that cells with defects in this pathway are hypersensitive to FBXO42 loss. Genome-wide CRISPR knockout screen (genetic epistasis/synthetic lethality) bioRxivpreprint Low bio_10.1101_2025.04.22.649889

Source papers

Stage 0 corpus · 3 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 m6A Regulator Expression Segregates Meningiomas Into Biologically Distinct Subtypes. Frontiers in oncology 4 35004283
2026 RNAseq-based meta-analyses revealed tumor suppressor-inducer fusion events in liver, oral, and ovarian cancer in the Indian population: a cancer cell surviving mechanism. Nucleosides, nucleotides & nucleic acids 0 41661231
2025 MZT2B promotes malignant phenotypes in NSCLC cells by enhancing mitochondrial function and COX5B expression. Cell death & disease 0 41213905

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