Hashimoto Y, Niikura T, Ito Y, Sudo H, Hata M, Arakawa E, Abe Y, Kita Y, Nishimoto I. Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults. J Neurosci. 2001 Dec 1;21(23):9235-45.
Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6336-41.
Hashimoto Y, Ito Y, Niikura T, Shao Z, Hata M, Oyama F, Nishimoto I. Mechanisms of neuroprotection by a novel rescue factor humanin from Swedish mutant amyloid precursor protein. Biochem Biophys Res Commun. 2001 May 4;283(2):460-8.
MEDICAL SCIENCES. For the article 窶廣 rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and A ホイ窶? by Yuichi Hashimoto, Takako Niikura, Hirohisa Tajima, Takashi Yasukawa, Haruka Sudo, Yuko Ito, Yoshiko Kita, Masaoki Kawasumi, Keisuke Kouyama, Manabu Doyu, Gen Sobue, Takashi Koide, Shoji Tsuji, Jochen Lang, Kiyoshi Kurokawa, and Ikuo Nishimoto, which appeared in number 11, May 22, 2001, of Proc. Natl. Acad. Sci. USA (98, 6336窶?6341), the following should be noted. First, the GenBank accession no. of HN cDNA is AY029066, not YA029066. Second, the authors admit that the paper lacked sufficient discussion regarding the implications of the findings. There is no proof that the HN cDNA represents a gene, that its origin is nuclear, or that the HN peptide is produced in vivo. The information that the long HN cDNA sequence is virtually identical to mitochondrial rRNA should have been put in the Discussion rather than published as supplementary material. The Discussion should have contained the following:
The long cDNA [1,567 bp including a poly(A) tail] containing the HN ORF is >99% identical (1548/1552) to positions 1679窶?3230 of mitochondrial DNA (GenBank accession no. AB055387).
Okamoto T, Takeda S, Giambarella U, Murayama Y, Matsui T, Katada T, Matsuura Y, Nishimoto I. Intrinsic signaling function of APP as a novel target of three V642 mutations linked to familial Alzheimer's disease. EMBO J. 1996 Aug 1;15(15):3769-77.
Yamatsuji T, Matsui T, Okamoto T, Komatsuzaki K, Takeda S, Fukumoto H, Iwatsubo T, Suzuki N, Asami-Odaka A, Ireland S, Kinane TB,Giambarella U, Nishimoto I. G protein-mediated neuronal DNA fragmentation induced by familial Alzheimer's disease-associated mutants of APP. Science. 1996 May 31;272(5266):1349-52.
Ikezu T, Okamoto T, Komatsuzaki K, Matsui T, Martyn JA, Nishimoto I. Negative transactivation of cAMP response element by familial Alzheimer's mutants of APP. EMBO J. 1996 May 15;15(10):2468-75.
Yamatsuji T, Okamoto T, Takeda S, Murayama Y, Tanaka N, Nishimoto I. Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype. EMBO J. 1996 Feb 1;15(3):498-509.
Nishimoto I, Okamoto T, Matsuura Y, Takahashi S, Okamoto T, Murayama Y, Ogata E. Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o) Nature. 1993 Mar 4;362(6415):75-9.
RachelN says, "One of the very interesting things about the interaction of APP and C100 with N-Pak is that it ties in with Nishimoto's work showing activation of Go"
KieranB says, "Is there some interaction between N-Pak and Go?"
RachelN says, "yes."
DavidS says, "I would like to get an exact idea of what your model is. Can you piece it all together, G0, PAK, APP etc. ?"
JohnW says, "How does N-Pak and Go interact simultaneously with C100?"
RachelN says, "It is known that N-Pak is immediately downstream of beta/gamma subunits of activated G proteins like Go."
DavidS says, "What binds to what and how do they work in sequence?"
RachaelN says, "this is what we need to know, and we would appreciate help from anyone who has experience with kinases. I think that APP probably does not bind directly to Go, because Nishimoto has never shown to my satisfaction that it does. However, I do think he's correct that APP activates Go in some way. I think that APP activates Go ...let me think a moment."
DavidS smiles broadly
RachaelN says, "it is possible that APP binds to N-Pak only when it activates the beta/gamma subunit of Go. That is my present working hypothesis."
RachaelN says, "Nishimoto has a paper in press showing that the apoptotic effects of APP mutants (FAD) are mediated through the beta/gamma unit of Go."
RachaelN says, "I find this intresting because one endpoint of N-Pak activating is known to be apoptosis."
Nonetheless, it remains possible that HN cDNA represents a nuclear transcribed mRNA and that the HN peptide is a natural product. Long regions of the HN cDNA are >99% identical to certain registered human mRNAs [1545/1553 at positions 14-1580 of FLJ22981 fis cDNA (AK026634), 925/929 at positions 1-929 of FLJ22517 fis cDNA, 914/919 at positions 1348-2266 of FLJ20341 fis cDNA, and 345/346 at positions 1-346 of PNAS-32 mRNA]. PNAS-32 mRNA is actually expressed to produce NB4 apoptosis-related protein, showing that this mRNA is transcribed from a nuclear gene. In addition, HN cDNA is highly similar to regions of more than 1,000 bp on human chromosomes [positions 245364-244075 of chromosome 11 draft sequence (92%, 1198/1290), positions 65752-66775 of chromosome X draft sequence (95%, 974/1025), and positions 687598-688608 of chromosome 5 draft sequence (93%, 954/1016)]. Also, the HN ORF has a Kozak-like sequence, although it is not canonical.
Suzuki A, Obata S, Hayashida M, Kawano H, Nakano T, Shiraki K. SADS: A new component of Fas-DISC is the accelerator for cell death signaling and is downregulated in patients with colon carcinoma. Nat Med. 2001 Jan;7(1):88-93. Retracted publication.