| RRC ID |
65650
|
| Author |
Ichikawa T, Shanab O, Nakahata S, Shimosaki S, Manachai N, Ono M, Iha H, Shimoda K, Morishita K.
|
| Title |
Novel PRMT5-mediated arginine methylations of HSP90A are essential for maintenance of HSP90A function in NDRG2low ATL and various cancer cells.
|
| Journal |
Biochim Biophys Acta Mol Cell Res
|
| Abstract |
N-myc downstream-regulated gene 2 (NDRG2) as a tumor suppressor is frequently downregulated in human T-lymphotropic retrovirus (HTLV-1)-infected adult T-cell leukemia (ATL) and variety of cancers, and negatively regulates PI3K signaling pathways through dephosphorylation of PTEN with protein phosphatase 2A (PP2A). We recently identified that protein arginine methyltransferase 5 (PRMT5) is one of novel NDRG2 binding proteins and the knockdown of PRMT5 induces cell apoptosis with degradation of several signaling molecules. To investigate how the apoptosis is induced by the knockdown PRMT5 expression, heat shock protein 90 alpha (HSP90A) was identified as a binding protein for NDRG2 or PRMT5 by immunoprecipitation-mass analysis. NDRG2/PP2A complex inhibited arginine methyltransferase activity of PRMT5 through dephosphorylation at Serine 335 (S335); however, in NDRG2low ATL-related cells, highly phosphorylated PRMT5 at S335 was mainly localized in cytoplasm with binding to HSP90A, resulting in enhancing arginine-methylation at the middle domain (R345 and R386). Since knockdown of PRMT5 expression or forced expression of HSP90A with alanine replacement of R345 or R386 induced apoptosis with the degradation of client proteins in NDRG2low ATL-related and other cancer cells, we here identified that the novel arginine methylations of HSP90A are essential for maintenance of its function in NDRG2low ATL and other cancer cells.
|
| Volume |
1867(2)
|
| Pages |
118615
|
| Published |
2020-2-1
|
| DOI |
10.1016/j.bbamcr.2019.118615
|
| PII |
S0167-4889(19)30223-X
|
| PMID |
31765670
|
| MeSH |
Adaptor Proteins, Signal Transducing / metabolism
Apoptosis
Arginine / metabolism
Carboxylic Ester Hydrolases / metabolism
Cell Line, Tumor
HSP90 Heat-Shock Proteins / antagonists & inhibitors
HSP90 Heat-Shock Proteins / genetics
HSP90 Heat-Shock Proteins / metabolism*
Humans
Leukemia-Lymphoma, Adult T-Cell / metabolism
Leukemia-Lymphoma, Adult T-Cell / pathology
Methylation
Phosphorylation
Protein Binding
Protein-Arginine N-Methyltransferases / antagonists & inhibitors
Protein-Arginine N-Methyltransferases / genetics
Protein-Arginine N-Methyltransferases / metabolism*
Proteolysis
RNA Interference
RNA, Small Interfering / metabolism
Tumor Suppressor Proteins / metabolism*
|
| IF |
4.105
|
| Resource |
| Human and Animal Cells |
SAS(RCB1974) |
