Abstract
The six regulatory non-redundant ATPases in the base of the 19 S regulator of the 26 S proteasome belong to the AAA superfamily of ATPases. Yeast two-hybrid genetic screens, biochemical analyses and cell biological studies have identified and characterized new interactors of the human S6 (rpt3) and S8 (rpt6) ATPases of the 19 S regulator of the 26 S proteasome. The S6 ATPase interacts with gankyrin. This protein is found in purified human 26 S proteasomes and in a smaller complex(es) containing CDK4 and free S6 ATPase. Gankyrin overexpression causes the phosphorylation of the retinoblastoma protein (pRb) and the release of E2F transcription factor to trigger the expression of DNA synthesis genes. Gankyrin is oncogenic in nude mice and is overexpressed in hepatocellular carcinoma cells (HCCs). The S8 ATPase interacts with members of the large Homer-3 protein family. There are three Homer genes; the Homer 1 and 2 gene products control trafficking and calcium-store-related functions of metabotropic glutamate receptors (e.g. mGluR1α). Homer-3A11 by binding to the S8 ATPase brings mGluR1α to the 26 S proteasome for degradation. The degradation of mGluR1α is blocked by proteasomal inhibitors and by overexpression of the N-terminus of Homer which binds to the receptor. The S8 ATPase and mGluR1α are co-localized in Purkinje dendrites in rat cerebellum. The data are discussed in terms of the regulation of the cell cycle and glutaminergic receptor functions by the 26 S proteasome.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 470-473 |
| Number of pages | 4 |
| Journal | Biochemical Society Transactions |
| Volume | 31 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 1 2003 |
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Keywords
- Gankyrin
- Homer
- Metabotropic glutamate receptor
- Proteasomal ATPase
ASJC Scopus subject areas
- Biochemistry
Cite this
Proteasomal interactors control activities as diverse as the cell cycle and glutaminergic neurotransmission. / Rezvani, K.; Mee, M.; Dawson, S.; McIlhinney, J.; Fujita, J.; Mayer, R. J.
In: Biochemical Society Transactions, Vol. 31, No. 2, 01.04.2003, p. 470-473.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Proteasomal interactors control activities as diverse as the cell cycle and glutaminergic neurotransmission
AU - Rezvani, K.
AU - Mee, M.
AU - Dawson, S.
AU - McIlhinney, J.
AU - Fujita, J.
AU - Mayer, R. J.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - The six regulatory non-redundant ATPases in the base of the 19 S regulator of the 26 S proteasome belong to the AAA superfamily of ATPases. Yeast two-hybrid genetic screens, biochemical analyses and cell biological studies have identified and characterized new interactors of the human S6 (rpt3) and S8 (rpt6) ATPases of the 19 S regulator of the 26 S proteasome. The S6 ATPase interacts with gankyrin. This protein is found in purified human 26 S proteasomes and in a smaller complex(es) containing CDK4 and free S6 ATPase. Gankyrin overexpression causes the phosphorylation of the retinoblastoma protein (pRb) and the release of E2F transcription factor to trigger the expression of DNA synthesis genes. Gankyrin is oncogenic in nude mice and is overexpressed in hepatocellular carcinoma cells (HCCs). The S8 ATPase interacts with members of the large Homer-3 protein family. There are three Homer genes; the Homer 1 and 2 gene products control trafficking and calcium-store-related functions of metabotropic glutamate receptors (e.g. mGluR1α). Homer-3A11 by binding to the S8 ATPase brings mGluR1α to the 26 S proteasome for degradation. The degradation of mGluR1α is blocked by proteasomal inhibitors and by overexpression of the N-terminus of Homer which binds to the receptor. The S8 ATPase and mGluR1α are co-localized in Purkinje dendrites in rat cerebellum. The data are discussed in terms of the regulation of the cell cycle and glutaminergic receptor functions by the 26 S proteasome.
AB - The six regulatory non-redundant ATPases in the base of the 19 S regulator of the 26 S proteasome belong to the AAA superfamily of ATPases. Yeast two-hybrid genetic screens, biochemical analyses and cell biological studies have identified and characterized new interactors of the human S6 (rpt3) and S8 (rpt6) ATPases of the 19 S regulator of the 26 S proteasome. The S6 ATPase interacts with gankyrin. This protein is found in purified human 26 S proteasomes and in a smaller complex(es) containing CDK4 and free S6 ATPase. Gankyrin overexpression causes the phosphorylation of the retinoblastoma protein (pRb) and the release of E2F transcription factor to trigger the expression of DNA synthesis genes. Gankyrin is oncogenic in nude mice and is overexpressed in hepatocellular carcinoma cells (HCCs). The S8 ATPase interacts with members of the large Homer-3 protein family. There are three Homer genes; the Homer 1 and 2 gene products control trafficking and calcium-store-related functions of metabotropic glutamate receptors (e.g. mGluR1α). Homer-3A11 by binding to the S8 ATPase brings mGluR1α to the 26 S proteasome for degradation. The degradation of mGluR1α is blocked by proteasomal inhibitors and by overexpression of the N-terminus of Homer which binds to the receptor. The S8 ATPase and mGluR1α are co-localized in Purkinje dendrites in rat cerebellum. The data are discussed in terms of the regulation of the cell cycle and glutaminergic receptor functions by the 26 S proteasome.
KW - Gankyrin
KW - Homer
KW - Metabotropic glutamate receptor
KW - Proteasomal ATPase
UR - http://www.scopus.com/inward/record.url?scp=0037398130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037398130&partnerID=8YFLogxK
U2 - 10.1042/BST0310470
DO - 10.1042/BST0310470
M3 - Article
C2 - 12653665
AN - SCOPUS:0037398130
VL - 31
SP - 470
EP - 473
JO - Biochemical Society Transactions
JF - Biochemical Society Transactions
SN - 0300-5127
IS - 2
ER -