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
|
Resource |
Human and Animal Cells |
HSC-3(RCB1975)
HSC-4(RCB1902)
SAS(RCB1974) |