Human T-cell leukemia virus type 1 Tax oncoprotein induces and interacts with a multi-PDZ domain protein, MAGI-3.
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), whereas the closely related virus HTLV-2 has not been associated with such malignant conditions. HTLV-1 Tax1 oncoprotein transforms a rat fibroblast cell line (Rat-1) much more efficiently than does HTLV-2 Tax2. By using a differential display analysis, we isolated MAGI-3 as a Tax1-inducible gene in Rat-1 cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis confirmed that Tax1 induced MAGI-3 in Rat-1 cells. MAGI-3 has multiple PDZ domains and interacted with Tax1 but not Tax2 in 293T cells. The interaction of Tax1 with MAGI-3 was dependent on a PDZ domain-binding motif, which is missing in Tax2. The interaction of Tax1 with MAGI-3 altered their respective subcellular localization, and moreover, the interaction correlated well with the high transforming activities of Tax1 in Rat-1 cells relative to Tax2. MAGI-3 mRNA and the allied MAGI-1, but not MAGI-2, were expressed in HTLV-1-infected T-cell lines. Our results suggest that the interaction of Tax1 and MAGI-3 alters their respective biological activities, which may play a role in transformation by Tax1 as well as in the pathogenesis of HTLV-1-associated diseases.
Ohashi
Minako
M
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
Sakurai
Mamoru
M
Higuchi
Masaya
M
Mori
Naoki
N
Fukushi
Masaya
M
Oie
Masayasu
M
Coffey
Robert J
RJ
Yoshiura
Kenta
K
Tanaka
Yuetsu
Y
Uchiyama
Makoto
M
Hatanaka
Masakazu
M
Fujii
Masahiro
M
D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002472:Cell Transformation, Viral; D015870:Gene Expression; D016356:Gene Products, tax / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D051528:Guanylate Kinases; D015490:HTLV-I Infections / Q000209:etiology; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry / Q000472:pathogenicity*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D016356:Gene Products, tax; D012333:RNA, Messenger; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases