PMID- 20604806
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20161125
IS  - 1365-2443 (Electronic)
IS  - 1356-9597 (Linking)
VI  - 15
IP  - 8
DP  - 2010 Aug
TI  - Deletion of Herp facilitates degradation of cytosolic proteins.
PG  - 843-53
LID - 10.1111/j.1365-2443.2010.01422.x [doi]
AB  - Although intracellular stresses are believed to be involved in the process of 
      neurodegeneration, it is not fully understood how one stress/stress response 
      affects another. Herp is an endoplasmic reticulum (ER)-located membrane protein 
      proposed to function in ER-associated degradation (ERAD). Herp is strongly 
      induced by ER stress but rapidly degraded by proteasome. To elucidate the effect 
      of Herp expression on proteolytic stress caused by impairment of the 
      ubiquitin-proteasome system (UPS), we utilized 293T Herp knockdown (KD) cells and 
      F9 Herp knockout cells. Knockdown of Herp gene unexpectedly facilitated the 
      degradation of Parkinson's disease-associated cytosolic proteins such as 
      alpha-synuclein and its binding partner, synphilin-1, and improved cell viability 
      during proteasomal inhibition. A similar tendency was observed in F9 Herp 
      knockout cells transfected with synphilin-1. Herp temporarily bound to 
      alpha-synuclein, synphilin-1 and the E3 ligase SIAH1a during proteolytic stress 
      but not during ER stress. Furthermore, deletion of Herp enhanced the amount of 
      ubiquitinated protein in the cytosol during proteasomal inhibition, although it 
      did not affect the activity or expression of proteasome. These results suggest 
      that ERAD molecule Herp may delay the degradation of cytosolic proteins at the 
      ubiquitination step.
FAU - Miura, Hikari
AU  - Miura H
AD  - Department of Neuroanatomy, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Ishikawa 920-8640, Japan.
FAU - Hashida, Koji
AU  - Hashida K
FAU - Sudo, Hirofumi
AU  - Sudo H
FAU - Awa, Yoshitaka
AU  - Awa Y
FAU - Takarada-Iemata, Mika
AU  - Takarada-Iemata M
FAU - Kokame, Koichi
AU  - Kokame K
FAU - Takahashi, Tetsuya
AU  - Takahashi T
FAU - Matsumoto, Masayasu
AU  - Matsumoto M
FAU - Kitao, Yasuko
AU  - Kitao Y
FAU - Hori, Osamu
AU  - Hori O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100702
PL  - England
TA  - Genes Cells
JT  - Genes to cells : devoted to molecular & cellular mechanisms
JID - 9607379
RN  - 0 (Carrier Proteins)
RN  - 0 (HERPUD1 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (SNCAIP protein, human)
RN  - 0 (alpha-Synuclein)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (seven in absentia proteins)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Carrier Proteins/*metabolism
MH  - Cell Line
MH  - Cell Survival
MH  - Cytosol/*metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - *Gene Deletion
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Membrane Proteins/*deficiency/genetics/*metabolism
MH  - Nerve Tissue Proteins/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Ubiquitin-Protein Ligases/*metabolism
MH  - alpha-Synuclein/*metabolism
EDAT- 2010/07/08 06:00
MHDA- 2011/02/18 06:00
CRDT- 2010/07/08 06:00
PHST- 2010/07/08 06:00 [entrez]
PHST- 2010/07/08 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
AID - GTC1422 [pii]
AID - 10.1111/j.1365-2443.2010.01422.x [doi]
PST - ppublish
SO  - Genes Cells. 2010 Aug;15(8):843-53. doi: 10.1111/j.1365-2443.2010.01422.x. Epub 
      2010 Jul 2.