RRC ID 64580
Author Nakamura A, Kakihara Y, Funayama A, Haga K, Mikami T, Kobayashi D, Yoshida Y, Izumi K, Kobayashi T, Saeki M.
Title HEATR1, a novel interactor of Pontin/Reptin, stabilizes Pontin/Reptin and promotes cell proliferation of oral squamous cell carcinoma.
Journal Biochem Biophys Res Commun
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.
Volume 557
Pages 294-301
Published 2021-6-11
DOI 10.1016/j.bbrc.2021.04.021
PII S0006-291X(21)00617-3
PMID 33894417
MeSH 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
IF 2.985
Human and Animal Cells HSC-3(RCB1975) HSC-4(RCB1902) SAS(RCB1974)