HEATR1, a novel interactor of Pontin/Reptin, stabilizes Pontin/Reptin and promotes cell proliferation of oral squamous cell carcinoma

Biochem Biophys Res Commun. 2021 Jun 11:557:294-301. doi: 10.1016/j.bbrc.2021.04.021. Epub 2021 Apr 21.

Abstract

Pontin and Reptin are closely related proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They form a hetero-oligomeric complex, Pontin/Reptin, which is involved in protein stability and assembly of the protein complexes as a molecular chaperone. Overexpression of Pontin and Reptin in tumor cells has been reported and is implicated in the development of various cancers. However, the molecular mechanism of Pontin/Reptin function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we identify HEAT repeat-containing protein 1 (HEATR1) as a novel binding factor of Pontin/Reptin. Functionally, HEATR1 stabilizes Pontin/Reptin and positively regulates OSCC cell proliferation by activating mTOR and pre-rRNA synthesis. We also find that HEATR1 expression is markedly upregulated in tumor region of OSCC tissue. Hence, we propose that HEATR1 is involved in the regulation of mTOR and ribosome biogenesis as a potential protein stabilizer of Pontin/Reptin in OSCC.

Keywords: HEATR1; Oral squamous cell carcinoma; Pontin; Reptin; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, rRNA
  • Humans
  • Immunohistochemistry
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Protein Binding
  • RNA Interference
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • TOR Serine-Threonine Kinases / metabolism
  • Tandem Mass Spectrometry
  • Up-Regulation

Substances

  • Carrier Proteins
  • HEATR1 protein, human
  • Minor Histocompatibility Antigens
  • RNA-Binding Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, human
  • RUVBL2 protein, human