Regulation of the level of Vesl-1S/Homer-1a proteins by ubiquitin-proteasome proteolytic systems.
The vesl-1S/homer-1a gene is up-regulated during seizure and long term potentiation. Other members of the Vesl family, Vesl-1L, -2, and -3, are constitutively expressed in the brain. We examined the regulatory mechanisms governing the expression level of Vesl-1S protein, either an exogenously introduced one in COS7 or human embryonic kidney 293T cells or an endogenous one in rat brain neurons in cultures. In both cases, application of proteasome inhibitors increased the amount of Vesl-1S protein but not that of Vesl-1L, -2, or -3 protein. Deletion analyses revealed that the C-terminal 11-amino acid region was responsible for the proteolysis of Vesl-1S by proteasomes. Application of proteasome inhibitors promoted ubiquitination of Vesl-1S protein but not that of the Vesl-1S deletion mutant, which evaded proteasome-mediated degradation. These results indicate that ubiquitin-proteasome systems are involved in the regulation of the expression level of Vesl-1S protein.
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
H
H
Ageta
A
A
Kato
S
S
Hatakeyama
K
K
Nakayama
Y
Y
Isojima
H
H
Sugiyama
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D017931:DNA Primers; D005786:Gene Expression Regulation; D000072233:Homer Scaffolding Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics; D017384:Sequence Deletion; D014452:Ubiquitins / Q000378:metabolism*
D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D017931:DNA Primers; D000072233:Homer Scaffolding Proteins; D009097:Multienzyme Complexes; D009479:Neuropeptides; D011994:Recombinant Proteins; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex