-

. . .


2009

1.

2.

3.

4.

5.

6.

10

7.

17

8.

9.

20

20

10.

22

 -
1.
Henry Rudolf Schoenheimer
1940 .

.
50%
.
.

.
.
. ()

()


.

2.

.
, ,

, ,
.

, .

 Ca 2+.
,
.

, NAD+,
(
).

3.
.

.

.

120

, ,
--,
10 .
. ,
,
.

.

.

.
.

. ,

.

(min)

0.2

RNA I

1.3

2.0

4.0

PEP

5.0

118

GAPDH

130

130

LDH

130

130

4.

1.

,
,

ATP

1.

5.

50

.
pH 5
pH .
pH
.

.

.
.

.
Lys-Phe-Glu-Arg-Gln
(KFERQ) . KFERQ

(-) ,
, .

6.

.


.

.
76
-
NMR.
H 1
.

 4
-.

Lys48

1
C-. Lys48

.
, Arg-Gly-Gly,
.
Gly
- - .
,
- Lys48 .

, .

.

.


3.


E1 (Ubiquitin activating enzyme) (
2).
ATP,
. Ubiquitin activating enzyme) E1
210 kDa.
E1
E2. E2 (Ubiquiting conjugating enzyme) ( 3)
150 Cys.
E2 - . ,

.

E3. E3, (Ubiquitin protein
ligase)

180

kDa

E2 -
(isopeptide bond) ( 3).
E3 .
E2
.
E2
( 3). , 50
-
Lys48
.

 - 2,
.
E2
3.
.
Lys48 .

.


.

ATP, 1.5103 kDa,
-

.
C-
.

.
3
3
.

Cys8
8

2
E2 Arabidopsis. Cys88
.

E 3

(Ubiquitin)

UB-COOH

- . 1, 2 3
(Uboquitin activating enzyme)
.
3 .
3
() ().

 2
.

7.
,
. , 50

-. Lys-48
C ' .

2,
.

ATP

2.000 kDa, 26S

26S .
26S
20 10
22-34 kDa
5
C- , .

,

( 4).
ATP ,
.
-

.
,

10

4
26S
Xenopus, 25 .
26S 450x190
1.500 kDa.

8.
-

.
-
, Alexander
Varshavsky .
208 , ,
- . :
, , , , , .
- (N-end rule)
.

11

 ,
.

()

>20

>20

>20

>20

>20

>20

~0.5

~0.5

~0.17

~0.17

~0.05

~0.05

~0.05

~0.05

~0.03

-

. ,
(P), (E), (S)
(T), PEST- .

.

9.

2.

12

ATP

13

10.
1. The ubiquitin system: functions and mechanisms. Finlay, D., and Varshavsky, A.
Trends Biochem. Sci. 10, 343-347. (1985).
2. Ubiquitin-mediated pathways for intracellular proteolysis. Rechsteiner, M. Ann.
Rev. Cell. Biol. 3, 1-30 (1987).
3. Ubiquitin-mediated protein degradation. Hershko, A. J. Biol. Chem. 263, 1523715240 (1988).
4. The degradation signal in a short-lived protein. Bachmair A., and Varshavsky, A.
Cell 56, 1019-1032 (1989).
5. New perspecives on the structure and function of ubiquitin. Monia, B.P., et al.
Bio/Technology 8, 209-215 (1990).
6. Ubiquitin-conjugating enzymes: novel regulators of eucaryotic cells. Jentsch, S.,
et al. Trends Biochem. Sci. 15, 195-198 (1990).
7. Inhibition of the N-end rule pathway in living cells. Baker, R.T. and Varshavsky,
A. Proc. Natl. Acad. Sci. USA 88, 1090-1094 (1991).
8. Peptide sequences that target cytosolic proteins for lysosomal proteolysis. Dice,
F. Trends Biochem. Sci 15, 305-309 (1990).
9. Proteolysis proteasomes and antigen presentation. Goldberg, A.L., and Rock, K.L.
Nature 357, 375-379 (1992).
10. The ubiquitin system for protein degradation. Hershko, A., and Ciechanover, A.
Annu. Rev. Biochem. 61, 761-807 (1992).
11. The ubiquitin-proteasome proteolytic pathway. Ciechanover, A. Cell 79, 13-21
(1994).
12. Ubiquitin and intracellular protein degradation. Hochstrasser, M. Curr. Opin. Cell
Biol. 4, 1024-1031 (1992).
13. The ubiquitin-conjugation system. Jentsch, S. Annu. Rev. Genet. 26, 179-207
(1992).
14. The multicatalytic and 26 S proteases. Rechsteiner, M., Hoffman, L., and Dubiel,
W. J. Biol. Chem. 268, 6065-6068 (1993).
15. Proteasomes: multicatalytic proteinase complexes. Rivett, A.J. Biochem. J. 291,
1-10 (1993).

16. The N-end rule. Varshavsky, A. Cell 69, 725-735 (1992).

14