{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:54:28Z","timestamp":1791114868173,"version":"4.1.0"},"reference-count":39,"publisher":"Society for Neuroscience","issue":"46","license":[{"start":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T00:00:00Z","timestamp":1368489600000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2012,11,14]]},"abstract":"<jats:p>Wnt\/\u03b2-catenin is a neuroprotective pathway regulating cell fate commitment in the CNS and many vital functions of neurons and glia. Its dysregulation is linked to a number of neurodegenerative diseases. Wnt\/\u03b2-catenin is also a repressor of HIV transcription in multiple cell types, including astrocytes, which are dysregulated in HIV-associated neurocognitive disorder. Given that HIV proteins can overcome host restriction factors and that perturbations of Wnt\/\u03b2-catenin signaling can compromise astrocyte function, we evaluated the impact of HIV transactivator of transcription (Tat) on Wnt\/\u03b2-catenin signaling in astrocytes. HIV clade B Tat, in primary progenitor-derived astrocytes and U87MG cells, inhibited Wnt\/\u03b2-catenin signaling as demonstrated by its inhibition of active \u03b2-catenin, TOPflash reporter activity, and Axin-2 (a downstream target of Wnt\/\u03b2-catenin signaling). Point mutations in either the core region (K41A) or the cysteine-rich region (C30G) of Tat abrogated its ability to inhibit \u03b2-catenin signaling. Clade C Tat, which lacks the dicysteine motif, did not alter \u03b2-catenin signaling, confirming that the dicysteine motif is critical for Tat inhibition of \u03b2-catenin signaling. Tat coprecipitated with TCF-4 (a transcription factor that partners with \u03b2-catenin), suggesting a physical interaction between these two proteins. Furthermore, knockdown of \u03b2-catenin or TCF-4 enhanced docking of Tat at the TAR region of the HIV long terminal repeat. These findings highlight a bidirectional interference between Tat and Wnt\/\u03b2-catenin that negatively impacts their cognate target genes. The consequences of this interaction include alleviation of Wnt\/\u03b2-catenin-mediated suppression of HIV and possible astrocyte dysregulation contributing to HIV neuropathogenesis.<\/jats:p>","DOI":"10.1523\/jneurosci.3145-12.2012","type":"journal-article","created":{"date-parts":[[2012,11,14]],"date-time":"2012-11-14T17:47:52Z","timestamp":1352915272000},"page":"16306-16313","source":"Crossref","is-referenced-by-count":57,"title":["Human Immunodeficiency Virus Type 1 (HIV-1) Transactivator of Transcription through Its Intact Core and Cysteine-Rich Domains Inhibits Wnt\/\u03b2-Catenin Signaling in Astrocytes: Relevance to HIV Neuropathogenesis"],"prefix":"10.1523","volume":"32","author":[{"given":"Lisa J.","family":"Henderson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara 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