Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Basic-Leucine Zipper Transcription Factors / chemistry
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Basic-Leucine Zipper Transcription Factors / physiology*
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Cell Line
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Human T-lymphotropic virus 1 / metabolism*
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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Models, Biological
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Molecular Sequence Data
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Proteasome Endopeptidase Complex / chemistry
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Proteasome Endopeptidase Complex / metabolism
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Protein Structure, Tertiary
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Retroviridae Proteins
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Time Factors
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Transfection
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Ubiquitin / chemistry*
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Ubiquitination
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Viral Proteins / chemistry
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Viral Proteins / physiology*
Substances
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Basic-Leucine Zipper Transcription Factors
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HBZ protein, human T-cell leukemia virus type I
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Retroviridae Proteins
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Ubiquitin
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Viral Proteins
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JNK Mitogen-Activated Protein Kinases
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Proteasome Endopeptidase Complex
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ATP dependent 26S protease