γλώσσες
Σελίδες
Νομικός
5 5 : (ubiquitin); 1. ( nucleosome)
1
D . , DA . , ( , ) . D . [1] . D D.
8-7 [2] , .( 8-7) , D . , D . D.[2] ,
5
2
, Roger Kornberg 1974. Aaron Klug . . , . (3)2(4)2 2-2. D. , , . . , , D .[3] D , . , D. DA, . 1 , DA. , , . D D . D 200 bp 680 . D 100 . , D . , , , 104 . D. : 360 110 .
5
3
D. D . D , . D .[3] ( ) 30 nm.( 8-8) , ' . [2]
8-8. [2] D "" D . . D . , D "" , D (linker DNA), . ( 2. 2. 3 4) D 146 . "" D.[2] , . . , 100. "" ' "" D.
5
4
(FIGURE 10-20) D , D. ( ). D, . D, 200 ( 146 D D ). ( 60 ) D. [4]
( ) [5] ( ) : , 4 . , , . . , " ". , , 30 nm. 30 nm ( 2) ' , 1
5 .[4].
5
2. 1 . 11 nm ( 2) 1 , [6] D . , R D ; D;[7] , . , D . , R . ' ,
5 R D.[7]
6
D . . , . , . , .[7] D . , , . D , D, . . . . D . , ( , ) "" . D , R . "" D - .[7] - : . , - . - , DNA .
5
7
, ( HMG), . , HMG14/17 -
. HMGI/Y , , DNA, 1, - . HMG DNA. , DNA (q.v. SRY, enhanceosome ) -, , DNA . DNA DNA .[8] DNA . . DNA - (). , (DACs) . , K9 H3, (MTs) , .. K4 3 . K9 , .. 1, DNA (DNMTs), . DNA MBD. DNMTs HDACs MTs, . .[9]
5
8
- DNA. H3 H4 (Figure 8.7) H3 Lys4 (K4). DNA , . . () . ' , -. , S . . , .[10] - .
. . D 250 ms ( 3) 10-15 ms. D
5
9
. D.[11]
3. .
. SWI/SNF ISW ( 4) ( ).[11]
4.
5 - .
10
:
D
(SW).
.
(SWI/SNF).
D.[11] .
. , . : hsp70 (drosophila), , . .[11] : 1) D , 2) - . D .[11] .
. .
5
11
. . ( 1) . . .[11]
1. .
:
D .
.
.[11] .
R pol.
5
12
R ( 5) D 50 , 12 bp. D D . [11]
5. R D , D . D .( 6) R 30 bp D . 10 bp D. . ( D).[11]
5
13
6.
5
14
[1] [2]
Berg J., Tymoczko J., Stryer L., , , , 2005, . 984. Alberts, Bray, Johnson, Lewis, Raff, Roberts, Walter, , , .. , .291-292.
[3] [4]
Berg J., Tymoczko J., Stryer L., , , , 2005, . 986. Alberts, Bray, Johnson, Lewis, Raff, Roberts, Walter, , , .. , .293-294.
[5] [6]
Lodish H., Berk A., Matsudaira P.,..,Molecular Cell Biology, fifth ed.,. 425 ., , : : ,...2005, .10
[7]
Alberts, Bray, Johnson, Lewis, Raff, Roberts, Walter, , , .. , .311-312.
[8] [9].167.
Twyman R.M., Advanced Molecular Biology, bios scientific publishes, .37 Wolfgang Arthur Schulz, Molecular Biology of Human Cancers, Spinger 2005, Wolfgang Arthur Schulz, Molecular Biology of Human Cancers, Spinger 2005, .180. ., , 14/7/06, http://multimedia.biol.uoa.gr/media2005_06/karamanos_files/lobby0.htm
[10] [11]
5 2. (Ubiquitin)
15
. (Ubiquitination) ( Ubiquitylation) - ( ) . 1975 8,5 kDa . , '80 Aaron Ciechanover, Avram Hershko Irwin Rose 2004. , . (polyubiquitination), , . ( , )
.[1] , , ( ) . . MPF . , .(Figure 1244) [2]
5
16
[3] ( 1) 76
8500 DA. : 96% ( 3 76 ). : MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDY NIQKESTLHLVLRLRGG [1]
5
17
1.[4] , 1, ,( 2) 2, , 3.
2.[5] , 1 . . (C-
5
18
1. , 2. , 3 2 - -, . , : - 48 . .[5] . , . , . 1, 2 3. , 2 3. 3 , 2-3 .[5] ; . . - . 20 , 2 . , , , , , . 3 - . , , , , ( S). [6] . ,
5
19
(V) 3. p53 (Fig.2.11) D, . 3 90% . , , .[6]
[7] " - "
, , . :
-
de novo
. -
. mRNA . :
. . . , . (tab.2.1)
5
20
. , . . , , . . --, . .[8]
[9] , ; 26S . , . 26S : 20S, , 19S. 20S ( 3) 14 700 kd .[6]
5
21
3.[6] 14 . 7 . . . . . , . , .( 4) 20S . 19S, 700 kd 20 . 20S 26S.( 5,6)
5
22
5.[10]
Figure
8.
Binding and to its short
of
the
polyubiquitinated substrate to the 26S proteasome degradation subsequent peptides.
Illustration was kindly provided by Dr. Ed Yeh, M. D. Anderson Cancer Center, Houston, TX. ( 26S .) 4.[11] 19S . 19S ( ) - 230 , , . . , . , A 19S 20S,
5
23
. , 19S ;. . .[10]
6.[12]
5
24
.
[10] . . , , . F- (F: ) , . . -. F- , - (: ). , - , 3. 3 - F-. (Figure 43-10)[10]
5
25
[13] -. F- - 1- : , , .[10] . . . , . 28 .( 7)
5
26
7.[14] , , . , . . , , . , , , . . .[14]
8.[14]
5
27
( 8) . - hiS, . hiS hiF. 1 160 28% hiF; .coli. hiS, ( 9) , 14% .
9.[14] , .[14]
, . ( ) , . : , , Alzheimer arkinson ( ), ( , , Liddle ( , Na+ , ) . . ,
5
28
, .[15]
.
Von Hippel-Lindau
Angelman, UBE3,
(E3) 6-AP. (E3) VHL VHL . Liddle Na+ (ENaC) . [16]
Figure2 . E1 E2 .(Figure2) , E2 E3, 2 3. E3 , . E3, . [17] F -k:
- .( 10,11)
F-k
3 F-k ( F-k)
5 F-k: p50 p52
29
p105 p100 . () : 2 UBC4/5
SCF-rCP 3 (p105,p100)
10.[18]
- . , . , - HIV, lovastatin, , . cyclosporine
5
30
, -450 , : -, , . , rapamycin,
PA28, proteasome . rapamycin - G1 S , . , aclarubicin (aclacino-mycin ), vinblastine vincristine , , aclarubicin, . Aclarubicin, anthracycline, , . vinca vinorelbine (Navelbine), , , .[19]
11.[18]
5 . :
31
UPS,
C class I .( 12)
12.[18]
[1] [2]
http://en.wikipedia.org/wiki/Ubiquitin Alberts, Bray, Johnson, Lewis, Raff, Roberts, Walter, , , .. , .687.
[3]p.468.
Nelson L. D., Cox M. M., Lehninger Principles of Biochemistry, fourth ed., Berg J., Tymoczko J., Stryer L., , , , 2005, . 715. Berg J., Tymoczko J., Stryer L., , , , 2005, . 716. Berg J., Tymoczko J., Stryer L., , , , 2005, . 717. Krauss G., Biochemistry of Signal Transduction and Regulation, 3d ed., p.105. Krauss G., Biochemistry of Signal Transduction and Regulation, 3d ed., p.102. Krauss G., Biochemistry of Signal Transduction and Regulation, 3d ed., p.103. Berg J., Tymoczko J., Stryer L., , , , 2005, . 718.
[4] [5] [6] [7] [8] [9] [10]
5 [11]Ciechanover A., The Ubiquitin Proteolytic System, The Proceedings of the American Thoracic Society 3:21-31 (2006) 2006 The American Thoracic Society, http://pats.atsjournals.org/cgi/content/full/3/1/FIG17#FIG17
32
[12]p. 177.
Koolman J., Roehm K.H., Color Atlas of Biochemistry, second ed., Thieme, 2005, Murray K. R., Granner K. D., Mayes A. P., Rodwell W. V., Harpers Illustrated Biochemistry, twenty sixth ed., 2003, p.468. Berg J., Tymoczko J., Stryer L., , , , 2005, . 719. Nelson L. D., Cox M. M., Lehninger Principles of Biochemistry, fourth ed.,p.1077. http://en.wikipedia.org/wiki/Immunohistochemistry Aaron Ciechanover, The ubiquitinproteasome pathway: on protein death and cell life, The EMBO Journal (1998) 17, 71517160, doi: 10.1093/emboj/17.24.7151 ., , 14/7/2006, http://multimedia.biol.uoa.gr/media2005_06/sarris_files/lobby0.htm Robert Z. Orlowski and E. Claire Dees, The role of the ubiquitination-proteasome pathway in breast cancer: Applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer, Breast Cancer Res. 2003; 5(1): 17. Published online 2002 August 14. doi: 10.1186/bcr460.
[13] [14] [15] [16] [17] [18] [19]