Coiled-coil motif as a structural basis for the interaction of HTLV type 1 Tax with cellular cofactors.
Human T lymphotropic virus type 1 (HTLV-1) Tax is a multifunctional protein centrally involved in transcriptional regulation, cell cycle control, and viral transformation. The regulatory functions of Tax are thought to be mediated through protein-protein interaction with cellular cofactors. Previously we have identified several novel binding partners for Tax, including human mitotic checkpoint protein MAD1 (TXBP181), G-protein pathway suppressor GPS2 (TXBP31), and IkappaB kinase regulatory subunit IKK-gamma. Here we described two additional Tax partners, TXBP151 and TXBP121. A closer examination of the sequences of eight independent cellular Tax-binding proteins identified by us and others revealed that all of them share a single characteristic, a highly structured coiled-coil domain. We also noted that Tax and the Tax-binding coiled-coil proteins can homodimerize. Additionally, the same domain in Tax is responsible for interaction with different coiled-coil proteins. Taken together, our findings point to a particular coiled-coil structure as one of the Tax-recognition motifs. The interaction of Tax with a particular subgroup of cellular coiled-coil proteins represents one mechanism by which Tax dysregulates cell growth and proliferation.
Chun
A C
AC
Institute of Molecular Biology, The University of Hong Kong, Hong Kong.
Zhou
Y
Y
Wong
C M
CM
Kung
H F
HF
Jeang
K T
KT
Jin
D Y
DY
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D019281:Dimerization; D016356:Gene Products, tax / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C103316:GPS2 protein, human; D016356:Gene Products, tax; D047908:Intracellular Signaling Peptides and Proteins; C501384:MAD1L1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; C120635:TAX1BP1 protein, human; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human