TY - JOUR
T1 - Potential CRE suppression by familial Alzheimer's mutants of APP independent of adenylyl cyclase regulation
AU - Giambarella, Ugo
AU - Murayama, Yoshitake
AU - Ikezu, Tsuneya
AU - Fujita, Toshiro
AU - Nishimoto, Ikuo
N1 - Funding Information:
This work was supported in part by grants from the Mitsui Life Science Welfare Foundation, the Naito Foundation, the Japan Medical Association, Mitsukoshi Fund of Medicine 1996, Foundation for Total Health Promotion, the Tokyo Medical Association, Brain Science Foundation, the Ministry of Health and Welfare of Japan, the Ministry of Education, Science, and Culture of Japan and by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Drug ADR Relief, R and D Promotion and Product Review of Japan. We greatly thank Mark C. Fishman, T. Bernard Kinane, John T. Potts Jr., Yoshiomi and Yumi Tamai, and Etsuro Ogata for indispensable support; and Dovie Wylie, Lorraine Duda, Naomi Koda, and Tomo Yoshida for expert technical assistance.
PY - 1997/7/21
Y1 - 1997/7/21
N2 - In familial Alzheimer's disease (FAD), mutations to I, F, and G have been discovered at V642 in the neuron-specific version of the amyloid precursor protein APP695. It has been found that expression of each FAD mutant suppresses the transcriptional activity of the cAMP response element CRE in a Gα(o)-dependent manner in a COS cell done NK1 [Ikezu et al. (1996) EMBO J. 15, 2468-2475]. Here we show that adenylyl cyclase (AC) inhibition is probably not the prerequisite for this pathway. First, expression of each FAD mutant in NK1 cells had no effect on AC activity stimulated by cholera toxin and by mutationally activated Gα(s) although the same expression completely repressed the stimulated CRE. Second, a transfected activating mutant of Gα(o) inhibited CRE without detectable suppression of AC, whereas similarly transfected activating Gα(i2) inhibited both AC and CRE. Third, FAD mutant-induced inhibition occurred for CRE activity stimulated by dibutyryl cAMP. These data suggest that CRE suppression by FAD mutants of APP could occur independently of AC.
AB - In familial Alzheimer's disease (FAD), mutations to I, F, and G have been discovered at V642 in the neuron-specific version of the amyloid precursor protein APP695. It has been found that expression of each FAD mutant suppresses the transcriptional activity of the cAMP response element CRE in a Gα(o)-dependent manner in a COS cell done NK1 [Ikezu et al. (1996) EMBO J. 15, 2468-2475]. Here we show that adenylyl cyclase (AC) inhibition is probably not the prerequisite for this pathway. First, expression of each FAD mutant in NK1 cells had no effect on AC activity stimulated by cholera toxin and by mutationally activated Gα(s) although the same expression completely repressed the stimulated CRE. Second, a transfected activating mutant of Gα(o) inhibited CRE without detectable suppression of AC, whereas similarly transfected activating Gα(i2) inhibited both AC and CRE. Third, FAD mutant-induced inhibition occurred for CRE activity stimulated by dibutyryl cAMP. These data suggest that CRE suppression by FAD mutants of APP could occur independently of AC.
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U2 - 10.1016/S0014-5793(97)00753-9
DO - 10.1016/S0014-5793(97)00753-9
M3 - Article
C2 - 9257698
AN - SCOPUS:0030838905
SN - 0014-5793
VL - 412
SP - 97
EP - 101
JO - FEBS Letters
JF - FEBS Letters
IS - 1
ER -