Human T-cell leukemia virus type 1 HBZ protein bypasses the targeting function of ubiquitination.
Human T-cell leukemia virus type 1 (HTLV-1) encodes an antisense viral gene product termed HTLV-1 basic leucine-zipper factor (HBZ). HBZ forms heterodimers with c-Jun, a member of the AP-1 family, and promotes its proteasomal degradation. Although most proteasomal substrates are targeted for degradation via conjugation of polyubiquitin chains, we show that ubiquitination is not required for HBZ-mediated proteasomal degradation of c-Jun. We demonstrate that HBZ directly interacts with both the 26 S proteasome and c-Jun and facilitates the delivery of c-Jun to the proteasome without ubiquitination. HBZ acts as a tethering factor between the 26 S proteasome and its substrate, thereby bypassing the targeting function of ubiquitination. These findings disclose a novel viral strategy to utilize the cellular proteolytic system for viral propagation.
Isono
Osamu
O
Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Ohshima
Takayuki
T
Saeki
Yasushi
Y
Matsumoto
Jun
J
Hijikata
Makoto
M
Tanaka
Keiji
K
Shimotohno
Kunitada
K
D000595:Amino Acid Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012191:Retroviridae Proteins; D013997:Time Factors; D014162:Transfection; D025801:Ubiquitin / Q000737:chemistry*; D054875:Ubiquitination; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*
D050976:Basic-Leucine Zipper Transcription Factors; C479751:HBZ protein, human T-cell leukemia virus type I; D012191:Retroviridae Proteins; D025801:Ubiquitin; D014764:Viral Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease