UNIVERZITET U SARAJEVU PRIRODNOPRIROD NO- MATEMA MATEMATIČKI TIČKI FAKULTET ODSJEK ZA BIOLOGIJU
APOPTOZA I KANCER
SEMINARSKI RAD IZ PREDMETA MOLEKULARNA MOLEKULARNA BIOLOGIJA
STUDENTICA:
PREDMETNA PROFESORICA:
Sabaheta Ha!"a#"$
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/(/( UNUTAR7ELIJSKI MEHANIZAM APOPTOZE P&%e P&%e #a= #a=$e+ $e+",> ",>*&? *&? a*t"#a a*t"#a", ",aa .%&*a>.a .%&*a>.aa a ) *a>.ae *a>.ae &!e &!e b"t" b"t" " )=) )=)ta% ta%$e+ $e+",> ",>*" *" eha=" eha="a a(( I>t%a!" I>t%a!"#a= #a=,a ,a >) .&*a .&*aa+ a+aa a &+a" &+a" & "=)" "=)"%a=, %a=,aa a*t"#= a*t"#=&>t &>t"" "t&h&= "t&h&=%" %",a ,a *&,e *&,e &>+&ba &>+&baa,) a,) e+e*t&=>*" =&>a .%&te"="t&h%& ) "t&>&+ ?,e >e .%&te"="t&h%& #e),e " a*t"#"%a aa.t&% .%&te"= A.a'-1( O#a, "t&h&=%",a+=" .)t a*t"#a",e .%&*a>.aa ,e a>t).+,e= ) =a,#e$e b%&,) >+)a,e#a a*t"#a",e a.&.t&e *a*& b" >e a*t"#"%a+a "+" )ba+a " a.+"'""%a+a *a>.a=a *a>*aa( P%"+"*& &@te$e=,a DNK *&,e ta*&e% &!e &#e>t" & a.&.t&e .&t%eba= ,e .85 *&," a*t"#"%a t%a=>*%".",) ?e=a *&," >) .%&&t&%" &>+&baa=,a "t&h%&a " "t&h&=%",a( O#" .%&te"= .%".aa,) B+-/ .&%&"" .%&te"=a A+be%t> /00/( A.&.t&=" .%&&t&%" *a& >t& ,e ,e Ba .%&te"= ')*="&="@) 6
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" "t&h&=%",a( Z=aa,=a .&%&"a .%&te"=a %e?)+at&%a )=)ta%$e+",>*e a.&.t&e ,e " IAP e=?+( I=h"b"t&% &' a.&.t&>"> .%&te"=a( Za &#e .%&te"=e >e >at%a a "=h"b"@) a.&.t&) =a #a =a"=a: #e"#a=,e a =e*ee .%&*a>. =e* .%&*a>.ae ae " #e"#a= #e"#a=,e ,e a =e*e *a>.ae *a>.ae *a* *a*&& b" >e >.%",e >.%",e"+& "+& ">.&+, ">.&+,a#a= a#a=,e ,e =,"h&# =,"h&#&? &? ,e+&#a=,a( O#" .%&te"=" >) .%#&b"t=& .%&=ae=" *a& .%&te"= *&,e .%&)"%a,) &%ee=" #"%)>" *&," =a.aa,) "=>e*te *&," "h *&%">te *a*& b" >.%",e"+" "='""%a=) $e+",) a > e>a&)="@t" .%",e =e?& #"%)> a#%@" >#&, %e.+"*a",>*" %e.+"*a",>*" .%&e>>( Kaa >e " "t&h&=%", "t&h&=%",aa &t.)>t" "t&h%& a >e a*t"#"%a a*t"#"%a A.a'-1 A.a'-1 &>+&baa >e " .%&te"= *&," b+&*"%a IAP .%&te"= "e >e .&#e$a#a e'"*a>=&>t a*t"#a",e .%&e>a $e+",>*&? >a&)="@te=,a(
5( POREME7AJI POREME7AJI U PROCESU PROCESU APOPTOZE9 APOPTOZE9 NAST NASTANAK ANAK KANCER KANCEROGENIH OGENIH 7ELIJA
U*&+"*& U*&+"*& ) =e*&, & eta.a a.&.t&e a.&.t&e &e & "=a*t"#a",e "=a*t"#a",e ?e=a *&," >t")+"@) >t")+"@) a.&.t&) a.&.t&) .&%ee$a,a ) *a>*.a=&, * a>*.a=&, *a>*a" "+" >"=tee .%&te"=a *&," "=h"b"@) a.&.t&) $e+",a =e &!e & *%a,a &>t#a%"t" >#&,e >a&)="@te=,e te &+a" & *ata>t%&'a+="h .&>+,e"a .& &%?a="a( Te .&>+,e"e >e a="'e>t),) >t#a%a=,e $e+",a &t.&%="h =a a.&.t&) *&,e >e &?) be>*&=a=& ",e+"t" ",e+"t" " .%&+"'e%"%at" .%&+"'e%"%at"(( O#e $e+",e =a"#a,) =a"#a,) >e *a=e%&?e=" *a=e%&?e=" $e+",aa *&,e .&%e =e&?)$=&>t" >a&)="@te=,a "a,) .&%ee$e=e b%&,=e %)?e %e?)+a",>*e eha="e >+"*a 5(1( Fa*t&%" *&," &#&e & .&,a#e *a=e%a =a"#a,) >e *a=e%&?e=" " ) &%?a=") >e .%&)a#a,) *a*& b" >e @t& #"@e >a=a+& & =,"h&#&, )t,ea,) =a %ee$e=,e %e?)+at&%="h eha="aa a.&.t&e te e'"*a>=& ,e+&#a=,) =a ">te B&+ et a+ 1<<(
7
S+"*a 5(1( Sheat>*" .%"*a =a>ta=*a *a=e%&?e=e $e+",e "#&%: (>+"e>ha%e(=et (>+"e>ha%e(=et K+,)=& a %a)",e#a=,e eha="a =a>ta=*a *a=e%a b"+& ,e >.&=a#a=,e a =&?" t)&%" =a>ta,) " ,e=e $e+",e a=a+""%a=,e "=a*t"#a",e h%&&>&a( Ge=" *&," &#&e & .&,a#e *a=e *a= e%a %a =a" =a"#a, #a,)) >e &=* &=*&? &?e=" e=" " .&%e .&%e .&%e .&%ee$ e$a, a,aa a.& a.&.t .t&e &e .& .&,a ,a#a #a *a=e *a=e%a %a &!e &!e b"t" b"t" " .&>+,e"a #"%)>=&? ,e+&#a=,a( T)&%>*" #"%)>" "%e*t=& ",e=,a,) e*>.%e>",) a.&.t&t"*"h ?e= te= a ta, =a"= $e+",e a%a!e=e #"%)>"a &?) &b"t" >.&>&b=&>t be>*&=a=e .%&+"'e%a",e( Je=a & =a,e@$e ete*t&#a="h ab=&%a+=&>t" ) $e+",aa h)a=&? *a=e%a ,e )ta",a =a .85 t)&%->).%e>&%>*& ?e=)( M)ta",e =a &#& ?e=) )%&*),) .&#e$a=) &t.&%=&>t =a %a",a",) " he&te%a.e)t>*e a?e=>e( 5(1(TUMOR SUPRESORSKI GEN .85 T)&% >).%e>&%>*" ?e= .85 "a *%"t"=) )+&?) ) *&=t%&+" >ta="=&? %a>ta " &%!a#a=,) ?e=et>*e >tab"+=&>t" ( O#e a*t"#=&>t" .&>+,e"a >) "=,e="e a .85 >t#a%a tet%ae%e *&," >e #e!) a &%ee=" >+",e =a DNA " a*t"#"%a,) t%a=>*%".",)( G)b"t*& t)&% >).%e>&%>*e a*t"#=&>t" )t"%a=" )t"%a=" .%&te"=" .%&te"=" .85 &b"#a,) &b"#a,) &=*&?e=" .&te=",a+ .&te=",a+ @t& %e)+t"%a %e)+t"%a =e*&=t%&+"%a =e*&=t%&+"%a=" =" %a>t& $e+",a t)&%a( Ot*%"#e=a >) " #a >%&="*a ?e=a .85 .25 " .5 *&," .&*a),) #e+"*) >t%)*t)%=) >+"=&>t > ?e=& .85 a+" ')=*"&=a+=& #e+"*e %a+"*e( S#a t%" ?e=a "a,) #a .%&&t&%a @t& a,e=& > a+te%=at#=" "%e"#a=,e " a+te%=at" #=" .&et*& t%a=>+a",e a,e b%&,=e "&'&%e 8
.%&te"=a > %a+""t" ')=*",aa( Ta*& ?e=" .25 " .5 "a,) #%+& >+&!e=) >t%)*t)%) " *&"%a,) #",e >*)."=e "&'&%" .%&te"=a *&,e "a,) >).%&t=& ')=*"&=a+=& ,e+&#a=,e "&'&%e > t%a=>a*t"#a",>*" .&%),e TA.255 *&,e "a,) t)&% >).%e>&%>*& ,e+&#a=,e " "&'&%e be t%a=>a*t"#a",>*&? .&%),a N.255 > .&te=",a+=" &=*&?e=" ,e+&#a=,e *&,e ,e+),) *a& t%a=>&"=a=t=" "=h"b"t&%" TA.5 " "#+,e? t" .a .85( Nea#=& ,e )t#%e=& a " .85 >a%!" ,&@ ,ea= .%&&t&% te a &+a" & >"=tee #"@e>t%)*"h "&'&%" ",a ')=*",a =",e ,&@ ) .&t.)=&>t" ,a>=a(( I>t%a!"#a=,a +a=&#a .&%&"e .85 =a%&"t& =,"h&#"h e)>&b="h "=te%a*",a .%"&=",et $e %a>#,et+,a#a=,) )+&?e &#"h .%&te"=a ) =a>ta=*) " %a#&,) t)&%a Z&%"$ Z&%"$ et al /010( U .&*)@a,"a )="@ta#a=,a *a=e%&?e="h $e+",a ) &%?a=") #e+"*) )+&?) ,e &"?%a+a .&%&"a .%&te"=a "t&*"=a =a#a="h "=te%'e%&="a IFN( IFN ( I=te%'e%&=" >) b"+" .%#" h)a=" .%&te"= *&," *& ," >) >e .&*aa+" ,e+&t#&%="a ) te%a."," *a=e%a " b"+" >) e) .%#" .%&)*t"a DNK *&," >) >e *+"= *+ "=" "*" *" *& *&%" %">t >t"+ "+"( "( I=t I=te%' e%'e%& e%&=" =" & &?) ?) "> ">.&+ .&+,a ,a#a #at" t" a=t a=t"* "*a= a=e%& e%&?e ?e=& =& , ,e+ e+&#a &#a=, =,ee " "%e %e*t *t=& =& "+ "+"" &)+a & )+a", ",& & ") ")=& =&&)+ &)+at& at&%=" %="hh " a=t a=t"-a= "-a=?"& ?"&?e= ?e=>*" >*"hh &?& &?&#&%a #&%a ta* ta*&& @t& "% "%e*t e*t=& =& &@t &@te$) e$),) ,) .%&+"'e%a",) $e+",>*"h "'e%e=",a",a *a=e%&?e="h *a =e%&?e="h $e+",a( D"%e*t=" " "="%e*t=" e'e*t" "=te%'e%&=a %e)+t),) "=)*",& .&>eb="h ?e=a IFN >t")+">a="h ?e=a ISG( O#" ?e=" "a,) a.&.t&t"*) ')=*",) " )*+,)),) TNF-Q a.&.t&) "=)*),)$" +"?a= TRAILA.&/L Fa>Fa>L IAP a>&",at"#=" a>&", at"#=" 'a*t&%-1 AF-1 *a>.a)*a>.a)-6 6 *a>.a) *a>.a)-; -; >RNA a*t"#"%a=) a*t"#"%a=) .%&te"= *"=a) PKR /8A &+"?&ae="+at >"=teta) OAS *"=ae a*t"#at&%e >%t" DAP *"=a>e ?a+e*t"= < IFN %e?)+at&%=e 'a*t&%e IRF> .%&",e+&"t"=e +e)*e",a ?e=e PML " %e?)+at&%e IFN "=)"%a=e >%t" RID> Cha+a-Sa%*a% et al, /005( .
6( ZAKLJUČAK M&+e*)+a%=a b"&+&?",a *a& ?%a=a b"&+&?",e &%a ,&@ =a.%e&#at" *a*& b" >e ) .&t.)=&>t" >h#at"& .%&e> a.&.t&e " *a*& b" >#" =,e?&#" eha="" b"+" %a,a@=,e=" & *%a,a( A.&.t&a ,e &b+"* .%&?%a"%a=e $e+",>*e >%t" *&," >e ,a#+,a ) '""&+&@*" " .at&+&@*" .%&e>"a ) &%?a=")( A.&.t&a ,e &?%a="e=a =a .&,e"=a=e $e+",e *aa >aa $e+",a >.%&#&" .%&?%a"%a=) >%t t,( "#%@a#a >a&)b">t#& " =e ,a#+,a >e "='+aa",a( A.&.t&a &že =a>tat" b&? >+ab+,e=,a "+" "&>ta=*a .&"t" .&"t"#=" #="h h >"?=a+ >"?=a+aa .&t%eb= .&t%eb="h "h a .%ež"#+,a# "#+,a#a=, a=,ee $e+",a $e+",a "+" b& b&?? .%"a= .%"a=,a ,a =e?at =e?at"#= "#="h "h >"?=a+a >"?=a+a(( D&at=a "e=t"'"*a",a ?e=a " .%&te"=a *&," %e?)+"@) eha="a a.&.t&e te =,"h&#a .%a*t"=a 9
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8( SA3ETAK
A.&.t&a .%e>ta#+,a =&%a+a= '""&+&@*" .%&e> $e+",>*e >%t" *&," ,e =aa,a= " .&t%eba= ) &%?a=") a b" >e eb%"&=a+=" %a#&, &#",a& be .&%ee$a,a *a& &b%abe=" &?&#&% )*+a=,a=,e &@te$e="h " .&te=",a+=& &.a>="h $e+",a *&,e &?) .&>tat" *a=e%&?e=e te +"a $e+",a a%a!e="h #"%)>& " a b" &@+& & >a=a",e )ta",a )ta",a )%&*&#a="h &@te$e=,"a DNK . =a,#e$" )>.,eh =a .&+,) ")a# ")a#a=,a a=,a .%&e>a .%&e>a .&>t"? .&>t"?=)t =)t ,e "e=t" "e=t"'"* '"*a" a",& ,& ?e=a *&," *&=t%&+" *&=t%&+"@) @) a.&. a.&.t& t&)( )( O#" ?e= ?e="" >) "e=t "e=t"' "'"* "*&#a &#a=" =" .%" .%" .%&) .%&)a# a#a=, a=,)) =eat =eat&e &e Caenorhabdit Caenorhabditis is elegans elegans Ma).a Ma).a> > 1<00 1<00( ( T&*& &*& .%&)a#a=,a &t*%"#e=a >) t%" ?e=a *&,a "a,) *+,)=) )+&?) ) %e?)+a"," % e?)+a"," " "#%@a#a=,) a.&.t&e( D#a >) ?e=a =)!=a a b" &@+& & a.&.t&e: e-5 " e-6( T%e$" ?e= e-< ,e+),e *a& =e?at"#=" %e?)+at&% a.&.t&e( Da+,=,"" a=a+"aa )t#%e=& ,e a >) ?e=" a a.&.t&) =a#ee=e =eat&e >%&=" &="a *& &#,e*a a N&be+&#) =a?%a) a &#& &t*%"$e &b"+" >) S=e B%e==e% " J&h= " J&h= E( S)+>t&= /00/( S)+>t&= /00/( g&"=e. A.&.t&a ,e ) $e+"," >t%&?& *&=t%&+">a= .%&e> *&," =e &!e b"t" a)>ta#+,e= *aa a.&=e *&,e .%eth&e =&?&b%&,=e &%'&+&@*e " b"&he",>*e .%&,e=e *&,e >e &"t),) ) #") '%a?e=t"%a=&>t" h%&&>&>*e DNK *&=e=a",e " %a>.aa=,a h%&at"=a ) a+e '%a?e=te %a>.aa=,) e>>e=?e% RNK I ) *&=a="" >*#%e=&>t" "t&.+ae " .+aa eb%a=e $e+",e *&,e >e ",e.a,) ) *&a"$e =a#a=e a.&.t&t"*a t,e+a@a( S#a*a $e+",a ) >#& ?e=et"*& *&) .&>,e),e @"'%) a >#&,e .%a#&#%ee=& >a&)="@te=,e( Ta @"'%a =a+a" >e ) &b+"*) "=a*t"#"%a="h e="a .%&*a>.aa *&,e %ea?),) =a >"?=a+ > "?=a+ a $e+",>*& >a&)="@te=,e( I="",at&%>*e .%&*a>.ae .&>ta,) a)t&.%e&te&+"t"*" a*t"#=e *%& &#",a=,e .%&e>a čiji je da &*"a a =,e?&# .&eta* &+"?&e%"a",a( D&>aa ,e .&=at& a ) a*t"#a"," )e>t#),) b"aa.t"#=" .%&te"=i ) .&&$ *&,"h &+a" & '&%"% a=,a =&?&b%&,="h *&.",a >.e"'"="h .%&*a>.aa *&,e t#&%e *&.+e*> "+" a?%e?at( P%&*a>.aa ; "="",at&%>*a *a>.aa *&,a ,e ) *&=ta*t) >a %ee.t&%"a $e+",>*e >%t" a*t"#"%a >e *%& #a ",e.a=,a *&,a a+,e &#&e & '&%"%a=,a #e+"*e " a+e .&,e"="e %e+e '&%e *a>.ae(
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&>t#a%"t" >#&,e >a&)="@te=,e te &+a" & *ata>t%&'a+="h .&>+,e"a .& &%?a="a( Te .&>+,e"e >e a="'e>t),) >t#a%a=,e $e+",a &t.&%="h =a a.&.t&) *&,e >e &?) be>*&=a=& ",e+"t" " .%&+"'e%"%at"( O#e $e+",e =a"#a,) >e *a=e%&?e=" $e+",aa *&,e .&%e =e&?)$=&>t" >a&)="@te=,a "a,) .&%ee$e=e b%&,=e b% &,=e %)?e %e?)+a",>*e eha="e. Je=a & =a,e@$e ete*t&#a="h ab=&%a+=&>t" ) $e+",aa h)a=&? *a=e%a ,e )ta",a =a .85 t)&%->).%e>&%>*& ?e=)( M)ta",e =a &#& ?e=) )%&*),) .&#e$a=) &t.&%=&>t =a %a",a",) " he&te%a.e)t>*e a?e=>e( T)&% >).%e>&%>*" ?e= .85 "a *%"t"=) )+&?) ) *&=t%&+" >ta="=&? %a>ta " &%!a#a=,) ?e=et>*e >tab"+=&>t" ( O#e a*t"#=&>t" .&>+,e"a >) "=,e="e "= ,e="e a .85 >t#a%a tet%ae%e *&," >e #e!) a &%ee=" >+",e =a DNA " a*t"#"%a,) t%a=>*%".",)( G)b"t*& t)&% >).%e>&%>*e a*t"#=&>t" )t"%a=" .%&te"=" .85 &b"#a,) &=*&?e=" .&te=",a+ @t& %e)+t"%a =e*&=t%&+"%a=" %a>t& $e+",a t)&%a(
2( LITERAT RATURA
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Ba*e% A( J( M&&=e M&&=e A( H)?he> H)?he> J( L&ba%" L&ba%" D( J&h=>&= J&h=>&= R(J( a= Sa#"++ J( 1<<6( Me>a=?"a+ e++ a.&.t&>">: the a,&% eha="> '&% %e>&+)t"&= &' ?+&e%)+a% h.e%e++)+a%"t "= e.e%"e=ta+ e>a=?"a+ .%&+"'e%at"#e =e.h%"t">( The J&)%=a+ &' Me"a+ I=#e>t"?at"&=( <68 /108-/112(
5( B&+ R( Te%)h+ Te%)h+e= e= P( P( a= MC&=*e MC&=*e D( 1<<( A.&.t&>"> A.&.t&>"> Ca=e% Ca=e% a= Ca=e% The%a. The%a.(( S)%?"a+ O=&+&?( 25 155-16/(
11
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Cha=? Cha=? D( D( "=? Z( "=? Z( Ca.a"& Ca.a"& ( Pete% ( a= a=? a=? ( /005( I=te%"e% .%&e>>"=? eha="> &' .%&a>.a>e-; at"#at"&=( The EMBO J&)%=a+( //12: 615/616/(
8( Cha+a-Sa%*a% M( L"==e% M(J( L") (F (F(( "++"a> B(R( Se= G(C( S"+#e%a= R(H( a= B&%e B& %e= = E( E(C( C( / /005 005( ( A.&.t&>"> a= "=te%'e%&=>: R&+e &' "=te%'e%&=->t")+ate "= te%'e%&=->t")+ate ?e=e> a> e"at&%> &' a.&.t&>">( A.&.t&>">: A= "=te%=at"&=a+ ,&)%=a+ &= .%e?%ae e++ eath( ;5 /5-/6<( 2( C&& C&&.e% .e% G( a= Ha) Ha)>a >a= = R( /006( /006( The Ce++: Ce++: A M&+e)+ M&+e)+a% a% A..%&a A..%&ah h th"% e"t"&= e"t"&=(( The Ae%"a= S&"et '&% M"%&b"&+&?( a>h"=?t&=( a>h"=?t&=(
12
