Fusion of Doppel to octapeptide repeat and N-terminal half of hydrophobic region of prion protein confers resistance to serum deprivation.
Our previous studies have shown an essential role played by the octapeptide repeat region (OR) and the N-terminal half of hydrophobic region (HR) in the anti-apoptotic activity of prion protein (PrP). As PrP-like protein Doppel (Dpl), which structurally resembles an N-terminally truncated PrP, did not show any anti-apoptotic activity, we examined apoptosis of HpL3-4 cells expressing Dpl fused to various lengths of the N-terminal region of PrP to investigate whether the PrP/Dpl fusion proteins retain anti-apoptotic function. HpL3-4 cells expressing Dpl fused to PrP(1-124) with the OR and N-terminal half of HR of PrP showed anti-apoptotic function, whereas Dpl fused to PrP(1-95) with OR did not rescue cells from apoptotic cell death induced by serum deprivation. These results indicate that the OR and N-terminal half of HR of PrP retains anti-apoptotic activity similar to full-length PrP.
Lee
Deug-chan
DC
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
Sakudo
Akikazu
A
Kim
Chi-kyeong
CK
Nishimura
Takuya
T
Saeki
Keiichi
K
Matsumoto
Yoshitsugu
Y
Yokoyama
Takashi
T
Chen
Shu G
SG
Itohara
Shigeyoshi
S
Onodera
Takashi
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003470:Culture Media; D058851:GPI-Linked Proteins; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018621:PrPC Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011328:Prions / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D014162:Transfection
D003470:Culture Media; D058851:GPI-Linked Proteins; D018621:PrPC Proteins; D011328:Prions; C122036:Prnd protein, mouse; D011993:Recombinant Fusion Proteins