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and 180 to give an apparent molecular weight of 105 kDa (Hofmann et al. 2000;
Ahn et al. 2001). Mutation of lysine residues 175 and 180 negatively affects the
efficiency of early viral promoter activation, but sumoylation is not required for
viral growth (Lee and Ahn 2004). The IE86 protein is phosphorylated in vitro by
the extracellular regulated kinase (ERK
)
and presumably affected in vivo by both
the mitogen activated protein kinase (MAPK
)
and ERK signal transduction
pathways in the infected cell (Harel and Alwine 1998; Heider et al. 2002). The IE86
protein is phosphorylated at multiple serine and threonine residues (Fig. 2a).
Mutation of the threonine residues at positions 27 and 233 or the serine residues at
positions 144 and 234 positively affects the efficiency of early viral promoter
activation (Harel and Alwine 1998). Deletion of the serine residues between 258
a
Early promotor
activation
Cell cycle
control
Autoregulation
of MIEP
T27
S144
T233 S234
P535,
Y537
Q548
K175 K180
1
258
275
85
552
579
H446
H452
AD
N
S
N
ZF
Core
AD
Autoregulation
DNA binding
Dimerization
TBP
TFIIB
b
human 509
CLPLMQKFPKQV
M
VRIFS
T-
N
Q
G
G
FMLPIYE
T
AAKAYAVGQFEQP
T
ET
PP
chimp 529
CLPLMQKFPKQV
M
LRIFS
T-
N
QS
SFMLPIYE
S
AAKAYAVGQFEEP
A
ET
T-
rhesus 552
L
VPLVQRFPKQV
A
IRIFT
NE
N
SN
SFMLPIYD
Q
AAK
M
YAVGQFEE
TK
D
---
AGM 514
L
IPLVQ
Q
YPKQV
A
IRIFS
AE
N
TS
SFMLPIYD
N
ASR
M
YAVGQFEEP
K
D
---
mouse 551
CL
H
L
S
Q
V
FPKQV
C
MRL
C
S
I-TG
G
LNP
LPIYE
ETVS
SY
VN
AQFE
ADDI
S
HH
rat 454
CI
QFA
Q
T
FPKN
AC
IRL
CNI-VG
G
LQP
LPIYE
KVVT
AY
TDT
QY
NFSPI
T
N
K
consensus 601 .....*..**.. .*... . ....****. ....*...*.... ..
human 558
EDLD
T
LSLAIE
A
AI
Q
DL
R
N
K
SQ
-
chimp 577
EDLD
T
LSMAIE
A
AIEDL
R
N
K
SQ
-
rhesus 599
EDL
AN
LSMAIE
K
AIEDM
N
Q
E
S
SQ
AGM 561
EELE
N
LSMAIE
E
AI
R
DM
QED
SQ
-
mouse 600
ED
YES
D
CE------
rat 503
D
SNGG
MS
TI
LD
QDS
D
SE------
consensus 651 .... ...... ..... . ..
ESG-----
E
Fig. 2
Functional domains of the HCMV IE86 protein.
a
Abbreviations:
AD
activation domain,
S
serine domain,
K
lysine,
T
threonine,
H
histidine,
P
proline,
Y
tyrosine,
Q
glutamine,
N
nuclear localization signal,
ZF
putative zinc finger.
b
Amino acid sequence alignment of pri-
mate and nonprimate IE86 protein homologs. Identical amino acid residues are shaded in black
and similar residues in gray. A
star
indicates a consensus sequence, and a
dot
a conserved
sequence. A
hyphen
designates a gap in the sequence. MultAlin was used for the alignment of the
IE86 residues for Towne strain (AAR31449), chimpanzee (NP612745), rhesus (AAB00488),
African green monkey (AAB16881), mouse (AAA74505), and rat (AAB92266)