| RRC ID |
54476
|
| Author |
Higuchi M, Tsubata C, Kondo R, Yoshida S, Takahashi M, Oie M, Tanaka Y, Mahieux R, Matsuoka M, Fujii M.
|
| Title |
Cooperation of NF-kappaB2/p100 activation and the PDZ domain binding motif signal in human T-cell leukemia virus type 1 (HTLV-1) Tax1 but not HTLV-2 Tax2 is crucial for interleukin-2-independent growth transformation of a T-cell line.
|
| Journal |
J Virol
|
| Abstract |
Human T-cell leukemia virus type 1 (HTLV-1) but not HTLV-2 is associated with adult T-cell leukemia, and the distinct pathogenicity of these two closely related viruses is thought to stem from the distinct biological functions of the respective transforming proteins, HTLV-1 Tax1 and HTLV-2 Tax2. In this study, we demonstrate that Tax1 but not Tax2 interacts with NF-kappaB2/p100 and activates it by inducing the cleavage of p100 into the active transcription factor p52. Using RNA interference methods, we further show that NF-kappaB2/p100 is required for the transformation induced by Tax1, as determined by the ability to convert a T-cell line (CTLL-2) from interleukin-2 (IL-2)-dependent to -independent growth. While Tax2 shows a reduced transforming activity relative to Tax1, Tax2 fused with a PDZ domain binding motif (PBM) present only in Tax1 shows transforming activity equivalent to that of Tax1 in CTLL-2 cells expressing an inducer of p52 processing. These results reveal that the activation of NF-kappaB2/p100 plays a crucial role in the Tax1-mediated transformation of T cells and that NF-kappaB2/p100 activation and PBM function are both responsible for the augmented transforming activity of Tax1 relative to Tax2, thus suggesting that these Tax1-specific functions play crucial roles in HTLV-1 leukemogenesis.
|
| Volume |
81(21)
|
| Pages |
11900-7
|
| Published |
2007-11-1
|
| DOI |
10.1128/JVI.00532-07
|
| PII |
JVI.00532-07
|
| PMID |
17715223
|
| PMC |
PMC2168800
|
| MeSH |
Amino Acid Motifs
Animals
Cell Line, Transformed
Cell Line, Tumor
Cell Transformation, Viral
Gene Products, tax / metabolism*
Human T-lymphotropic virus 1 / metabolism*
Human T-lymphotropic virus 2 / metabolism*
Humans
Interleukin-2 / metabolism*
Leukemia / pathology*
Leukemia / virology
Mice
NF-kappa B p52 Subunit / metabolism*
Protein Structure, Tertiary
T-Lymphocytes / metabolism*
|
| IF |
4.324
|
| Times Cited |
73
|
| Resource |
| DNA material |
CSII-EF-IRES-GFP (RDB17866)
CSII-EF-IRES2-Bsd (RDB17867)
CSII-EF-IRES-GFP-RfA (RDB17868)
CSII-EF-IRES2-Bsd-RfA (RDB17869)
CSII-EF-MCS (RDB04378)
CSII-CMV-MCS-IRES2-Bsd (RDB04385)
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
