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NEK2A regulates PLIN2 expression through a SERBP1 dependent pathway

Tomohiko Makiyama1, Toshihiro Aiuchi1, Tomoko Mikajiri1

  • 1Department of Biological Chemistry, Showa Medical University Graduate School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.

Iscience
|June 15, 2026
PubMed

Insights

Researchers found that NEK2A kinase regulates PLIN2 expression in liver cells. This pathway involves SERBP1 and impacts lipid metabolism regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Metabolic Regulation

Background:

  • Lipid droplets are central to cellular lipid metabolism.
  • Expression of the lipid droplet protein PLIN2 is crucial and tightly controlled.
  • Understanding PLIN2 regulation offers insights into metabolic diseases.

Purpose of the Study:

  • To identify novel regulators of PLIN2 expression.
  • To elucidate the molecular mechanisms controlling PLIN2 levels in human hepatoma cells.
  • To investigate the role of NEK2A in lipid droplet protein regulation.

Main Methods:

  • Utilized human hepatoma cell lines.
  • Performed gene depletion and overexpression studies of NEK2A.
  • Employed kinase-dead mutants and truncated NEK2A domains.
  • Conducted proteomic analysis to identify binding partners.
  • Assessed mRNA and protein levels of PLIN2.
  • Used PPARγ inhibitor to study pathway reversal.

Main Results:

  • NEK2A acts as a negative regulator of PLIN2 expression.
  • NEK2A's kinase domain, not its catalytic activity, mediates PLIN2 suppression.
  • SERBP1 is a NEK2A-binding partner essential for PLIN2 regulation.
  • NEK2A-SERBP1 pathway regulates PLIN2 independently of triacylglycerol levels.
  • PPARγ signaling is involved in the observed PLIN2 regulation.

Conclusions:

  • Identified a novel kinase-independent NEK2A-SERBP1 pathway regulating PLIN2.
  • This pathway provides new insights into lipid droplet protein regulation beyond lipid storage.
  • Findings contribute to understanding the complex control of lipid metabolism.
Keywords:
biochemistrybiological scienceshealth sciencesmetabolomicsmolecular biology

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