Regolazione della traduzione
•generale
•specifica
Initiation Factor
Activity
eIF-1
Fidelity of AUG codon recognition
eIF-1A
Facilitate Met-tRNAiMet binding to small subunit
eIF-2
Ternary complex formation
eIF-2B (GEF)
GTP/GDP exchange during eIF-2 recycling
eIF-3 (10 subunits) Ribosome subunit antiassociation, binding to 40S subunit
eIF-4F (4E, 4A, 4G) mRNA binding to 40S, ATPase-dependent RNA helicase activity
eIF-4A
ATPase-dependent RNA helicase
eIF-4E
5' cap recognition
eIF-4G
Scaffold for of eIF-4E and -4A in the eIF-4F complex
eIF-4B
Stimulates helicase, binds simultaneously with eIF-4F
eIF-4H
Similar to eIF4B
eIF-5
Release of eIF-2 and eIF-3, ribosome-dependent GTPase
eIF5B
Subunit joining
eIF-6
Ribosome subunit antiassociation
Via delle MAP chinasi
stress
Chinasi di eIF2a
Figure 3.
Stress-Responsive eIF2 Kinases Inhibit General Translation yet Stimulate Expression of a Special Class of Genes
(A) Architecture of the four eIF2 Ser-51 kinases. The conserved kinase domains (KD) are depicted in green. The two hemebinding sites in HRI are marked in red. The dsRNA binding domains (dsRBD) in PKR are shown in blue. The N-terminal half
of PERK resembles the corresponding domain of the ER stress-responsive IRE1 kinase. Also indicated are signal peptide
(SP) and transmembrane (TM) domain of PERK. The regulatory histidyl-tRNA synthetase (HisRS) domain in GCN2 is shown
in purple. The locations of the N-terminal GCN1 binding domain (blue), charged region (+/-), and pseudokinase domain (KD),
as well as the C-terminal ribosome binding and dimerization domain (RB/DD) in GCN2 are also indicated. The activating
condition or ligand for each kinase and the known sources of the kinases are also indicated.
Azione delle chinasi di eIF2a
Stress-Responsive eIF2 Kinases Inhibit General Translation yet Stimulate Expression of a Special Class of Genes
(B) Stress response pathway for regulation of translation by eIF2 phosphorylation. The eIF2 kinases phosphorylate eIF2 leading to
inhibition of eIF2B (red bar). This results in low levels of ternary complex (gray arrow) resulting in reduced general translation (gray
arrow) and increased translation of GCN4, ATF4, or certain isoforms of C/EBP (black arrow). Increased production of the
transcription factors GCN4, ATF4, or C/EBP results in increased expression of their target genes.
Regolazione eIF2a

Fosforilazione su ser 51 in risposta a stress da
parte di 4 chinasi: PKR, GCN2, PERK, HRI

La fosforilazione impedisce il riciclo da parte di
eIF2B

La traduzione di alcuni mRNA è stimolata da bassi
livelli di eIF2a attivo

Molti virus hanno sistemi per impedire la
fosforilazione di eIF2a
eIF4F
Regolazione eIF4E

Fosforilazione su ser 209 da parte di Mnk1 (e
Mnk2) correlata con attivazione

Mnk interagiscono con eIF4G e sono attivate dalla
via delle MAP chinasi

eIF4E è inibito dall’interazione con 4E-BP (1, 2 e 3)

4E-BP sono inibite da fosforilazione dipendente
dalla via di mTOR