Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199
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Transcript of Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199
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8/14/2019 Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199
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N T @ E @ B G J Y G Y K T
Xlk gbx`ytnj`oktgx`k tnjk no KTE A! flgbbkjv `b tgxnvxkndjgvx`f fkjjv
Jknbgthn Lktbgbhks A` Ln Ygta Vl`-W`be Fg` J`be W`b B`fnjg Ygtxt`hek Okhkt`fn Vkvx`
Y{dj`vlkh nbj`bk3 79 Mgp 4995
Vyt`bekt Vf`kbfk!D{v`bkvv Mkh`g D"_" 4995
Gdvxtgfx Uk tkyntx nb xlk tnjk no A! f{ttkbxv `b xlk
mkflgb`vmv tke{jgx`be xlk ytnj`oktgx`nb no [MT 79?-97nvxkndjgvx f nvxknvgtfnmg fkjjv" Kjkfxtnylpv`njne`fgj
gbgjpv`v vlnukh xlgx [MT 79?-97 fkjjv ytnh{fk tnd{vx
A! f{ttkbxv xlgx fgb dk ylgtmgfnjne`fgjjp vkygtgxkh `bxn
xun mgcnt fnmynbkbxv3 g K-8967-v{vfkyx`djk f{ttkbx*
@K-8967* gbh g xkxtgkxlpjgmmnb`{m ,XKG)-v{vfkyx`djk
fnmynbkbx* @XKG" Ukvxktb djnx gbh TX-YFT gbgjpv`v
vlnukh xlgx @K-8967 `v ytnh{fkh dp kxlkt g en-en ,kge)-
tkjgxkh flgbbkjv ,KTE)" @bf{dgx`nb no xlk fkjjv u`xl K-
8967 kblgbfkh xlk`t ytnj`oktgx`nb dp
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x{mnt fkjj j`bkv no h`ooktkbx vykf`kv ,l{mgb gbh m{t`bk)
gbh h`vx`bfx l`vxnekbkv`v ,bk{tndjgvxnmg* tlgdhnmpnvgt-
fnmg* ghkbnfgtf`bnmg* j{be m`ftnfpxnmg* y x{`xgtp
x{mntv* `bv{j`bnmg dkxg-fkjjv* gbh mnbndjgvx`f jk{akm`g)
Q;* ?* 79* 4;* 86* 8?* ;7]" Kkb xln{el ynxgvv`{m flgbbkjv
gtk gd{bhgbx `b dnbk fkjjv* xlk`t tnjk `b hkxktm`b`be dnbk
hkkjnymkbxg fnmyjk| ytnfkvv ul`fl `v tke{jgxkh dp
m{jx`yjk ogfxntv `bfj{h`be lnmkndn| xtgbvft yx`nb ogfxntv*etnuxl ogfxntv ,OEO* _KEO* DMYv* @EO)* xtgbvft yx`nb
ogfxntv ,T{b|4* Vn|)* lntmnbkv ,EL* YXL) mgxt`| mk-
xgjjnytnxk`bgvkv* ytnxk`b a`bgvkv* `xgm`b H* vk| vxktn`hv
gbh fgjf`{m Q77]`v ynntjp {bhktvxnnh" Xn kj{f`hgxk xlk
tnjk no ynxgvv`{m flgbbkjv `b xlk mkflgb`vmv xlgx hkxkt-
m`bk xlk ytnj`oktgx nb no dnbk x`vv{k uk flgtgfxkt`skh
ynxgvv`{m f{ttkbxv k|ytkvvkh `b [MT 79?-97 nvxkndjgvx`f
nvxknvgtfnmg fkjjv" Lktk uk vlnu xlgx `bl`d`x nb no
kbhnekbn{v KTE flgbbkjv dp xlk fjgvv @@@ gbx`gttlpxlm`f
fnmyn{bh* K-8967* jkghv xn g v`eb`fgbx `bftkgvk `b xlk
ytnj`oktgx`nb no xlk fkjjv" Uk o{txlkt vlnu xlgx xlk m`xn-
ekb`f kookfx no K-8967 `bnjkv xlk gfx`gx`nb no fgjf`{m-hkykbhkbx ygxlugpv xltn{el xlk `bl`d`x nb no xlk KTE
flgbbkjv" Xgakb xnekxlkt xlkvk bh`bev {bhktvfntk bku
tnjkv no KTE A! flgbbkjv `b dnbk x`vv{k fkjjv gbh ytn`hk
gb {bk|ykfxkh `bv`elx `bxn xlk f{ttkbx `ku no xlk mkfl-
gb`vmv enktb`be ytnj`oktgx`nb no dnbk"
Mkxlnhv
Fkjj f{jx{tk
Fkjjv uktk mg`bxg`bkh `b Kgejkv m`b`mgj kvvkbx`gj
mkh`{m ,[MT 79?-97) nt m`b`m{m kvvkbx gj mkh`{m
gjylg ,FLN) v{yyjkmkbxkh u`xl 79+ ,.) okxgj dn`bk
vkt{m yj{v ;9 {b xv.mj ykb`f`jj`b* gbh ;9 je.mj vxtkyxn-
mpf`b ,V`emg)" Xlk fkjjv uktk vkkhkh `b 6;-mm h`vlkv
gx 79*999 fkjj.fm4 `b xlk vgmk mkh`{m nt xlk vgmk
mkh`{m u xl xkvx ht{ev" K-8967 h`lphtnfljnt`hk ugv
y{tflgvkh otnm Xnft`v Fnnavnb @bf"* XKG-Fj ugv otnm
V`emg gbh `nbnmpf`b otnm Gjk|`v D`nflkm`fgjv" @o bnx
nxlktu`vk vxgxkh mkh`g ,u xl nt u`xln{x ht{ev) ugv tk-
yjgfkh kktp 48 l" Goxkt h`ekvx nb u xl xtpyv`b fkjjv
uktk tkv{vykbhkh `b MKM gbh xlkb uktk fn{bxkh {v`beg dt`elx j`bk fn{bx`be flgmdkt" Ont kjkfxtnylpv`njnep*
fkjjv uktk vkkhkh nbxn ynjp-J-jpv`bk-xtkgxkh ejgvv fn-
ktvj`yv gx g hkbv`xp no 79*999 fkjjv.fm4"
Kjkfxtnylpv`njnep
Hgxg uktk tkfnthkh u`xl gb G|nygxfl 499D ,G|nb) g YF
,Hkjj) gbh Fjgmyk| vnoxugtk ,G|nb)* jxktkh gx
of = 7 aLs gbh vgmyjkh gx 4"; aLs" Gdn{x ;79 MU
ygxfl y`ykxxkv uktk y{jjkh {v`be g Ojgm`be-Dtnub y{jjkt
,V{xxkt* FG)" Dgxl vnj{x`nb ugv ,`b mM) 6 AFj* 789
BgFj* 79 Lkykv ,ghc{vxkh xn yL 5"? u xl BgNL)* 4";
FgFj4* gbh 7"9 MeFj4" Y`ykxxk vnj{x`nb ugv ,`b mM) 789
AFj* 79 Lkykv ,ghc{vxkh xn yL 5"6 u xl ANL)* 7"9
MeFj4* 7"9 FgFj4* gbh 77 KEXG ,ghc{vxkh xn yL 5";
u`xl ANL)" Ulnjk-fkjj f{ttkbxv uktk knakh dp njxgek c{myv no gt`gdjk gmyj`x{hk gbh h{tgx`nb ,gv vykf`kh `b
xlk xk|x) otnm g lnjh`be ynxkbx gj no
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D`nflkm`vxtp
[MT 79?-97 gbh FLN fkjjv uktk ugvlkh u xl 79 mj
`fk-fnjh YDV gbh jpvkh u`xl r4 mj `fk-fnjh T@YG d{ookt
,;9 mM Xt`v yL 5"8* 7;9 mM BgFj* 7 mM KHXG* 7+
@EKYGJ FG-?69* 9";+ ,u.) hkn|pflnjgxk* 9"7+ ,u.)
VHV* otkvljp ghhkh 79 mM `nhngfkxgm`hk* ylnvylgxgvk
gbh ytnxkgvk `bl`d xntv ont 69 m`b gx 8F" Fkjj jpvgxkvuktk fkbxt`o{ekh ont ?9 m`b gx 8F gbh xlk v{yktbgxgbx
ugv `bf{dgxkh `b VHV vgmyjk d{ookt gx r090;F ont
7; m`b* djnxxkh gbh vxg`bkh u`xl tgdd`x ynjpfjnbgj gbx -
LKTE gbx`dnhp ,V`emg) h j{xkh ,73;99) ont 7"; l"
Mkmdtgbkv uktk fgtko{jjp ugvlkh gbh vxg bkh u xl
vkfnbhgtp gbx`dnh`kv ont Ukvxktb `v{gj sgx`nb"
TX-YFT
mTBG ugv k|xtgfxkh otnm [MT 79?-97 fkjjv {v`be
Xt` tkgekbx ,V`emg) onjjnukh dp TX-YFT gv hkvft`dkhytk`n{vjp Q6;]" Xlk YFT ytnh{fx ugv gmyj`kh {v`be
yt`mktv ,;-FEXFXXFGFGFFEXGFXFEEF-6 gbh ;-
FFGEGEFFGGGEGXEGEFGEE-6 ) fflgba`be g vxtkxfl
no 4?7 dy dkxukkb xlk vkfnbh gbh on{txl xtgbvmkmdtgbk
hnmg`bv no tgx KTE" Xlk YFT ytnh{fx ugv fjnbkh `b xlk
XNYN kfxnt ,@b`xtnekb) gbh fnbtmkh dp g{xnmgxkh
HBG vkw{kbf`be"
Hkxktm`bgx`nb no fgjf`{m gbh ytnxk`b fnbxkbx
[MT 79?-97 fkjjv uktk yjgxkh nb ?9 mm x`vv{k f{jx{tkyjgxkv gx g hkbv`xp no
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m`hyn`bx ont njxgek gfx`gx`nb gbh g vjnyk ogfxnt* _7.4 =
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fnbxt`d{x`nb no @XKG xn xlk ytnj oktgx`nb no xlk fkjjv"
O`e{tk 8D vlnuv xlgx ytnetkvv`k `bftkgvk no xlk fnb-
fkbxtgx`nb no XKG `b xlk mkh`g ytnyntx`nbgjjp `myg`tkh
xlk ytnj`oktgx`nb no xlk fkjjv" @b fnbxtgvx bk xlkt 49 jM
K-8967 bnt 7 mM XKG lgh gbp kookfx nb xlk ytnj`oktg-
x`nb no xlk FLN fkjjv ,hgxg bnx vlnub)" Nxlkt dtngh-
vykfxt{m A! flgbbkj djnfaktv v{fl gv 8-gm`bnypt`h`bk
,8-GY) gjvn `myg`tkh xlk ytnj`oktgx nb no [MT 79?-97
fkjjv ,O`e" 8F)" Lnukkt 8-GY `bl`d`xkh xlk ytnj`oktgx`nb
no FLN fkjjv `bh`fgx`be xlgx `xv kookfxv fn{jh bnx dk gv-
ft`dkh xn vykf`f `bl`d`x`nb no A! flgbbkjv gv `b xlk fgvk
no K-8967 gbh XKG" Xlk kookfxv no XKG gbh K-8967 uktk
ghh`x`k ,O`e" 8H)" Xl{v* xlk hkftkgvk `b ytnj oktgx nb
fg{vkh dp 9"6 mM XKG fn{jh dk tkvf{kh dp 49 jM
K-8967 gbh fkjjv ytnj`oktgxkh vj`elxjp dkxxkt xlgb {bxtkgxkh
fkjjv1 o{txlkt `bftkgvk `b xlk XKG fnbfkbxtgx`nb `bl`d`xkh
ytnj oktgx`nb kkb `b xlk ytkvkbfk no K-8967" Xlkvk
ndvktgx`nbv v{eekvx tvx* xlgx g XKG-vkbv`x k gbh g
K-8967-vkbv`x k flgbbkj ytkvkbx `b [MT 79?-97 fkjjv
fgb gookfx ytnj`oktgx`nb `b nyynv`xk ugpv gbh vkfnbh*
xlgx xlk mkflgb`vmv {bhktjp be xlk`t m xnekb`f gbh
gbx`m`xnekb`f gfx`nb gtk h`vx`bfx"
@bl`d`x`nb no @K-8967 `v gvvnf`gxkh u`xl fkjj
hkynjgt`sgx`nb gbh gjxktkh fgjf`{m lnmknvxgv`v
@b mgbp fkjj xpykv* A! flgbbkjv ytnmnxk ytnj`oktgx`nb dp
tke{jgx`be fgjf`{m `bffl{|kv xltn{el xlk fnbxtnj no xlk
mkmdtgbk ynxkbx`gj* xlktkontk uk `bkvx`egxkh ulkxlkt xl`v
ekbktgj mkflgb`vm ugv tkvynbv`djk ont xlk @K-8967-mkh`gxkh
O`e" 4 D`nylpv fgj flgtgfxkt vx`fv no @K-8967 f{ttkbxv" ,G) [MT
79?-97 ulnjk-fkjj f{ttkbxv `b xlk gdvkbfk gbh `b xlk ytkvkbfk no
49 jM K-8967 `b xlk dgxl vnj{x`nb" Xlk K8967-vkbv`x`k fnmynbkbx`v ndxg`bkh dp v{dxtgfx`be xlk xnxgj f{ttkbx otnm xlk {bdjnfakh f{ttkbx
,t`elx)" ,D) Tkytkvkbxgx`k ulnjk-[MT 79?-97 fkjj f{ttkbx knakh dp
tkykx`x`k njxgek c{myv otnm
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kookfxv nb xlk ytnj`oktgx nb no [MT 79?-97 fkjjv" Xlk
nykb`be no A! flgbbkjv ytnh{fkv g f{ttkbx xlgx mnkv xlk
mkmdtgbk ynxkbx gj xnugth xlk kw{`j`dt`{m ynxkbx gjno ynxgvv`{m gffnth`be xn Kw" 6" @o K-8967 `bl`d`x @A* xlk
fnbh{fxgbfk ont ynxgvv`{m* EA* flgbekv gffnth`be xn3
EA EAmg|
7 ht{e=A bL;
ulktk EAmg| `v g fnbvxgbx gbh A gbh bL lgk xlk {v{gj
mkgb`bev" Xlk mkmdtgbk ynxkbx gj* _m* flgbekv dp H_3
H_ @A
Em
EA
EA E_A _m ?
ulktk xlk mkmdtgbk fnbh{fxgbfk Em = EA ! E `v
k|ytkvvkh gv xlk v{m noEAgbh no gjj nxlkt `nbv* E* gbh _A`v xlk kw{`j`dt`{m ynxkbx`gj ont ynxgvv`{m" Xn `bkvx`egxk
ulkxlkt xlk ytkvkbfk no K-8967 `b xlk dgxl vnj{x`nb gjxktkh
xlk mkmdtgbk tkvx`be ynxkbx`gj ,MTY) gbh.nt xlk fnbfkb-
xtgx nb no fpxnvnj`f fgjf`{m* uk kmyjnpkh xlk ygxfl-
fjgmy xkflb`w{k `b xlk f{ttkbx fjgmy fnbe{tgx`nb gbh
o{tg-4 m`ftnffl{nt`mkxtp" O`e{tk ;G vlnuv xlgx gyyj`fgx`nb
no 49 jM K-8967 ,g jkkj v{of`kbx xn `bl`d x xlk
fnttkvynbh`be vkbv`x`k fnbh{fxgbfk) h`h bnx hkynjgt`sk
xlk fkjjv ulkb xlk k|xktbgj fnbfkbxtgx`nb no A! ugv
ylpv`njne`fgj ,6 mM) gbh xlk fnmyn{bh gjvn og jkh xn
o{txlkt hkynjgt`sk xlk mkmdtgbk `b vpmmkxt`fgj vnj{x`nbv
,789 mM* hgxg bnx vlnub)" @b fnbxtgvx* gyyj`fgx`nb no
; mM XKG fg{vkh v`eb`fgbx hkynjgt`sgx`nb ,r79 m_*
hgxg bnx vlnub)" Flgbe`be xlk fnbfkbxtgx`nb no A! otnm
jnu ,6 mM) xn l`el ,789 mM) gbh `fk ktvg h`h bnx
knak fgjf`{m-mkh`gxkh ffl{ntkvfkbfk k`xlkt `b xlk gdvkbfk
O`e" 8 Kookfxv no 8-GY* XKG gbh K-8967 nb xlk ytnj oktgx`nb no
[MT 79?-97 fkjjv" [MT 79?-97 gbh FLN fkjjv uktk yjgxkh gx
79*999 fkjjv.fm4 hkbv xp gx hgp 9 gbh uktk fn{bxkh gx 48-l
`bxktgjv" Hgxg gtk bntmgj`skh xn xlk mg| m{m gj{k `b fnbxtnj
,bntmgj skh ytnj`oktgx`nb)" ,G) Ytnj`oktgx`nb no [MT 79?-97 `b
fnbxtnj fnbh`x`nbv ,f`tfjkv) nt u`xl xlk ghh x`nb no xlk onjjnu`befnbfkbxtgx`nbv no K-8967 `b xlk mkh`g ,`b jM)3 79 ,xt`gbejkv)* 49
,vw{gtkv)" @bvkx3 mg|`m{m ytnj oktgx`nb ktv{v K-8967 fnbfkbxtg-
x`nb" Hgxg gtk otnm < k|ykt`mkbxv" ,D) [MT 79?-97 fkjjv `b xlk
gdvkbfk.ytkvkbfk no xlk onjjnu`be fnbfkbxtgx`nbv no XKG `b xlk
mkh g ,`b mM)3 9 ,f tfjkv)* 9"7 ,vw{gtkv)* 9"6 ,xt gbejkv)* 7"9
,h`gmnbhv)" Hgxg gtk otnm 8 k|ykt`mkbxv" ,F) Ytnj`oktgx`nb no [MT
79?-97 ,f`tfjkv) gbh FLN fkjjv ,xt`gbejkv) `b fnbxtnj fnbh x`nbv nt
u`xl xlk ghh`x`nb no 79 mM 8-GY ,lnjjnu vpmdnjv) `b xlk f{jx{tk
mkh`g" Hgxg gtk otnm 8 k|ykt`mkbxv" ,H) Ytnj`oktgx`nb no [MT 79?-
97 fkjjv gx hgp 5 `b xlk gdvkbfk ,h`gmnbhv) nt ytkvkbfk ,vw{gtkv) no
49 jM K-8967 gbh no xlk `bh fgxkh XKG fnbfkbxtgx`nbv" Hgxg gtk
otnm 8 k|ykt`mkbxv
O`e" 6 KTE `v hkxkfxkh `b [MT 79?-97 fkjjv" ,G) Ukvxktb djnx
`v{gj`sgx`nb u`xl gbx`-LKTE gbx`dnh`kv no FLN fkjjv ,jgbk 7) gbh
[MT 79?-97 fkjjv ,jgbk 4) jpvgxkv" Xlk gbx dnh`kv hkxkfxkh g
r749 aHg dgbh ul`fl fnttkvynbhv xn xlk mnjkf{jgt uk`elx no KTE
nbjp `b [MT 79?-97 jpvgxkv" Xlk mgtakt ugv DkbflMgta ,@b`xtn-
ekb)" ,D) Gv `b ,G) ont FLN fkjjv ,jgbk 7) nt [MT79?-97 fkjjv`bf{dgxkh ; hgpv u`xl ,jgbk 4) nt u`xln{x ,jgbk 6) 79 jM K-8967" Xn
gffn{bx ont xlk K-8967-hkykbhkbx ytnj`oktgx`nb xlk fkjjv uktk fn{bxkh
gbh gb gyytn|`mgxkjp kw{gj b{mdkt no fkjjv ugv {vkh" , F) TX-YFT
tkkgjv xlk ytkvkbfk no KTE `b [MT 79?-97 fkjjv" mTBG ugv
k|xtgfxkh otnm [MT 79?-97 fkjjv {v`be Xt` tkgekbx ,V`emg) onjjnukh
dp TX-YFT" Xlk YFT ytnh{fx vlnub `b jgbk 7 ,r4
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nt `b xlk ytkvkbfk no K-8967 ,O`e" ;D* b = 8 k|ykt`mkbxv)"
Xlk og`j{tk no K-8967 xn kj f`x flgbekv `b xlk MTY nt
fgjf`{m `bxgak ugv ytndgdjp g fnbvkw{kbfk no xlk ogfx xlgx
K-8967 djnfa`be `v vxgxk-hkykbhkbx" Nb xlk nxlkt lgbh fkjjv
gtk k|ykfxkh xn k|l`d`x nvf`jjgx`nbv `b xlk mgeb`x{hk no xlk
MTY h{t`be ygtx`f{jgt ylgvkv no xlk`t fpfjk" Ont `bvxgbfk*
`x `v xln{elx xlgx mkmdtgbk lpyktynjgt`sgx`nb `bh{fkh dp
xlk nykb`be no A! flgbbkjv lkjyv xlk xtgbv`x`nb xnugth xlkE7 ylgvk `b vkktgj fkjj xpykv Q;4]" @x `v ynvv`djk xlgx xlk
`bl`d`xntp gfx`nb no K-8967 xgakv yjgfk h{t`be nbk no xlkvk
ylgvkv gbh v`bfk djnfa`be `v `ttkktv`djk* xl`v vln{jh tkv{jx
`b yktmgbkbx hkynjgt sgx`nb" Xn ghhtkvv xl v yn`bx uk
mkgv{tkh xlk tkvx`be ynxkbx gj `b fkjjv `bf{dgxkh u`xl
K-8967 nkt ? hgpv" Fkjjv xtkgxkh u`xl K-8967 uktk mntk
hkynjgt`skh xlgx {bxtkgxkh fkjjv ,O`e" ?G* K-8967-G)"
Fnbv`vxkbx u`xl xlk bnx`nb xlgx ytnjnbekh njxgek vx`m{-
jgx`nb `b xlk ytkvkbfk no K-8967 `bh{fk fkjj hkynjgt`sgx`nb*
xlk MTY ugv mkgv{tkh dkontk gbh goxkt kna`be KTE
f{ttkbxv dp g xtg`b no 69 hkynjgt`s`be vxkyv xn !?9 m_" Gv
k|ykfxkh* xlk MTY ugv r74+ mntk ynv`x`k ,b = ;) goxktnjxgek-vx`m{jgx`nb ,O`e" ?G* K-8967-@)" Xn kgj{gxk
xlk fnbfkbxtgx`nb no fgjf`{m `b fnbxtnj fkjjv nt `b fkjjv
`bf{dgxkh u`xl K-8967 ont v`| fnbvkf{x`k hgpv uk {vkh g
a`x xlgx kmyjnpv g m`| no fgjf`{m-vkbv`x`k hpkv ,W{gbx`-
FltnmXM* D`ngvvgp Vpvxkmv* Lgpugth* FG)" Oj{ntkvfkbfk
mkgv{tkmkbxv uktk bntmgj`skh ont xlk ytnxk`b fnbxkbx no
xlk xnxgj jpvgxkv* ul`fl uk gvv{mkh xn dk ytnyntx`nbgj xn
xlk b{mdkt no fkjjv" Fnbv`vxkbx u`xl n{t ytk`n{v tkv{jxv*
xlk fgjf`{m fnbxkbx `b fkjjv `bf{dgxkh u`xl K-8967 ugv
v`eb`fgbxjp `bftkgvkh ,O`e" ?D)" @o KTE flgbbkjv tke{jgxkfgjf`{m `bffl{|* xlk ytkvkbfk no g fgjf`{m `nbnylntk* ul`fl
mgakv fgjf`{m-vkjkfx`k yntkv `b xlk yjgvmg mkmdtgbk*
vln{jh `bxktoktk u`xl xlk ytnj`oktgx`k kookfx no K-8967" Gv
k|ykfxkh* 799 be.mj `nbnmpf`b* g hnvk xlgx fn{jh dk
xnjktgxkh* `bxktoktkh u`xl xlk ytnj`oktgx`k gfx`nb no K-89673
fkjjv fn- bf{dgxkh u`xl `nbnmpf`b gbh 49 jM K-8967
ytnj oktgxkh jkvv xlgb fnbxtnj fkjjv ,O`e" ?F)" Xgakb
xnekxlkt xlkvk hgxg v{eekvx xlgx fgjf`{m-hkykbhkbx
ygxlugpv kblgbfk xlk ytnj`oktgx nb no xlk [MT 79?-97
fkjjv gbh kbhnekbn{v KTE flgbbkjv `bl`d x xlkvk
ytnfkvvkv"
H`vf{vv`nb
Kjkfxtnylpv`njne`fgj* mnjkf{jgt gbh d`nflkm`fgj k`hkbfk
v{yyntx xlk bnx`nb xlgx kge-tkjgxkh A! flgbbkjv* gtk
k|ytkvvkh `b gbh k|ktx gb gbx`ytnj`oktgx`k kookfx nb [MT
79?-97 fkjjv" Xlkvk fkjjv ytnh{fk tnd{vx njxgek-hkykbhkbx
A! f{ttkbxv xlgx fgb dk ylgtmgfnjne`fgjjp vkygtgxkh `bxn
xun mgcnt fnmynbkbxv3 g K-8967-v{vfkyx`djk f{ttkbx ul`fl
`v ytnh{fkh dp KTE gbh ul`fl fnbxt`d{xkv xn tn{eljp 4;+
xn @A* gbh g XKG-v{vfkyx djk fnmynbkbx gbh ulnvk
mnjkf{jgt `hkbx xp `v gx ytkvkbx {babnub" Ul jk @XKG `v
ytnj`oktgx`k* fnbv vxkbx u`xl xlk ukjj-kvxgdj vlkh tnjk no
A! flgbbkjv `b vx`m{jgx`be m`xnv`v Q4* 40* 64* 6
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8/14/2019 Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199
8/10
xlk ytnj`oktgx`nb no [MT 79?-97 fkjjv d{x u`xl nbk mgcnt
h`ooktkbfk3 xlgx xlk hkynjgt`sgx`nb-mkh`gxkh `bftkgvk `b
ytnj`oktgx`nb `v gfl`kkh gx xlk k|ykbvkv no g h`m`b`vlkh
KTE gfx``xp" G vkfnbh mgcnt h`ooktkbfk tkjgxkv xn xlkmkflgb`vmv tke{jgx`be fgjf`{m `bffl{| ul`fl `v akp xn fkjj
ytnj`oktgx`nb" @b l{mgb dtndjgvxv nt X-jpmylnfpxkv ont
k|gmyjk* fgjf`{m nvf`jjgx`nbv nff{t `b vpbfltnbp u`xl
mkmdtgbk f{ttkbxv Q66* 8 @b ul`fl ylgvkv no xlk fkjj
fpfjk `v xlk gfx``xp no A! flgbbkjv ft{f`gj ont ytnj`okt-
gx`nb> Xlkvk jgp glkgh gbh u`jj dk xlk mgxxkt no o{x{tk
`bkvx`egx`nbv"
Gfabnujkhekmkbxv Uk xlgba Htv" S{` Ygb* P{xgag L{tgxg gbh
C`gbc`k Mg ont lkjy u`xl m`ftnffl{nt`mkxtp* Ht" Cnlb Jkbgth ont ft`x`fgj
O`e" ? @bl`d`x`nb no @K-8967 gjxktv fgjf`{m lnmknvxgv`v" ,G)
Mkmdtgbk tkvx`be ynxkbx`gj no fnbxtnj fkjjv nt no fkjjv `bf{dgxkh ont
? hgpv u`xl 49 jM K-8967 ,K-8967-G) nt `b xlk ytkvkbfk no xlk vgmkfnbfkbxtgx`nb no K-8967 dkontk gbh goxkt njxgek-vx`m{jgx`nb dp g
xtg`b no 69 fnbvkf{x`k njxgek c{myv xn !?9 m_ ,otnm gb lnjh`be
njxgek no
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8/14/2019 Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199
9/10
tkgh`be no xlk mgb{vft`yx gbh F`bs`g Vkvx` ont lkjy u`xl xlk etgyl`fv"
Xl`v unta ugv v{yyntxkh dp gb B@L Etgbx T97EM? Fgbfkt Tkvkgtfl* ;
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8/14/2019 Hernandez Et Al Cell Biochemistry and Biophysics (2007) 47 (2) 199
10/10
65" Vflj flxkt* J" F"* Yglgy`jj* Y" G"* / Vfl{mgflkt* Y" G" ,7006)"
Tkf`ytnfgj tke{jgx`nb no A! flgbbkjv dp Fg4! `b `bxgfx l{mgb X
jpmylnfpxkv" Tkfkyxntv Flgbbkjv* 7,6)* 49747;"
6