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Zeta-crystallin: a moonlighting player in cancer

Matteo Lulli1, Daniele Nencioni2, Laura Papucci2

  • 1Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Università Degli Studi di Firenze, Viale G.B. Morgagni, 50, Firenze, 50134, Italy. matteo.lulli@unifi.it.

Cellular and Molecular Life Sciences : CMLS
|September 30, 2019
PubMed

Insights

Zeta-crystallin (ζ-crystallin) stabilizes mRNAs for metabolic processes and apoptosis resistance. This moonlighting protein may play a pivotal role in cancer by hijacking cellular acidity responses.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Crystallins are lens structural proteins, with zeta-crystallin (ζ-crystallin) being ubiquitously expressed and possessing enzymatic activity.
  • ζ-crystallin is a moonlighting protein with dual functions: mRNA binding and stabilization, and NADPH:quinone oxidoreductase activity.

Purpose of the Study:

  • To investigate the multifaceted roles of ζ-crystallin, particularly its potential involvement in cancer.
  • To explore how ζ-crystallin's known functions might be co-opted by cancer cells.

Main Methods:

  • Literature review and data mining from public databases.
  • Analysis of existing research on ζ-crystallin's mRNA binding and enzymatic activities.
  • Hypothetical framework construction based on gathered evidence.

Main Results:

  • ζ-crystallin stabilizes mRNAs involved in renal glutamine metabolism, aiding in metabolic acidosis compensation.
  • It also binds mRNAs for antiapoptotic proteins like Bcl-2 in leukemia cells.
  • The physiological role of its enzymatic activity remains unclear.

Conclusions:

  • ζ-crystallin is proposed as a potential key player in cancer.
  • Cancer cells may exploit ζ-crystallin to manipulate acidity responses, enhancing resistance to oxidative stress and apoptosis.
  • This hijacking supports cancer's reliance on glutamine metabolism.
Keywords:
Ammoniagenesis in cancerApoptosisCancer metabolismMetabolic acidosisRNA metabolism

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