Expression of a protein involved in bone resorption, Dkk1, is activated by HTLV-1 bZIP factor through its activation domain.

Retrovirology
Nicholas PolakowskiIsabelle Lemasson

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia, a malignancy characterized by uncontrolled proliferation of virally-infected CD4+ T-cells. Hypercalcemia and bone lesions due to osteoclast-mediated bone resorption are frequently associated with more aggressive forms of the disease. The HTLV-1 provirus contains a unique antisense gene that expresses HTLV-1 basic leucine zipper (bZIP) factor (HBZ). HBZ is localized to the nucleus where it regulates levels of transcription by binding to certain cellular transcriptional regulators. Among its protein targets, HBZ forms a stable complex with the homologous cellular coactivators, p300 and CBP, which is modulated through two N-terminal LXXLL motifs in the viral protein and the conserved KIX domain in the coactivators. To determine the effects of these interactions on transcription, we performed a preliminary microarray analysis, comparing levels of gene expression in cells with wild-type HBZ versus cells with HBZ mutated in its LXXLL motifs. DKK1, which encodes the secreted Wnt signaling inhibitor, Dickkopf-1 (Dkk1), was confirmed to be transcriptionally activated by HBZ, but not its mutant. Dkk1 plays a major role in the development of bone ...Continue Reading

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Citations

Mar 22, 2012·Nucleic Acids Research·Torsten WurmIsabelle Lemasson
Oct 14, 2011·Viruses·Nicholas PolakowskiIsabelle Lemasson
Apr 19, 2011·Journal of Molecular Biology·Pamela R CookIsabelle Lemasson
Jun 9, 2016·Reviews in Medical Virology·Wendy J van ZuylenCaroline E Ford
Oct 4, 2019·JCI Insight·Jingyu XiangKatherine N Weilbaecher
Oct 21, 2017·Oncotarget·Alison K EsserKatherine N Weilbaecher
Sep 3, 2016·Endocrine Reviews·Peter J TebbenRajiv Kumar
Aug 24, 2021·Frontiers in Cell and Developmental Biology·Pankaj TrivediMaria Pia Felli

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Methods Mentioned

BETA
nuclear translocation
PCR
transfection
glycosylation
acetylation
ChIP
immunoprecipitation
transfections
ELISA
biopsies

Software Mentioned

iQ5 Optical System

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