NUCKS1, a novel Tat coactivator, plays a crucial role in HIV-1 replication by increasing Tat-mediated viral transcription on the HIV-1 LTR promoter

Hye Young Kim, Byeong Sun Choi, Sung S. Kim, Tae Young Roh, Jihwan Park, Cheol Hee Yoon

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: Human immunodeficiency virus-1 (HIV-1) Tat protein plays an essential role in HIV gene transcription from the HIV-1 long terminal repeat (LTR) and replication. Transcriptional activity of Tat is modulated by several host factors, but the mechanism responsible for Tat regulation by host factors is not understood fully.Results: Using a yeast two-hybrid screening system, we identified Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) as a novel Tat-interacting partner. Here, we report its function as a positive regulator of Tat. In a coimmunoprecipitation assay, HIV-1 Tat interacted sufficiently with both endogenous and ectopically expressed NUCKS1. In a reporter assay, ectopic expression of NUCKS1 significantly increased Tat-mediated transcription of the HIV-1 LTR, whereas knockdown of NUCKS1 by small interfering RNA diminished Tat-mediated transcription of the HIV-1 LTR. We also investigated which mechanism contributes to NUCKS1-mediated Tat activation. In a chromatin immunoprecipitation assay (ChIP), knockdown of NUCKS1 interrupted the accumulation of Tat in the transactivation-responsive (TAR) region on the LTR, which then led to suppression of viral replication. However, NUCKS1 expression did not increase Tat nuclear localization and interaction with Cyclin T1. Interestingly, the NUCKS1 expression level was lower in latently HIV-1-infected cells than in uninfected parent cells. Besides, expression level of NUCKS1 was markedly induced, which then facilitated HIV-1 reactivation in latently infected cells.Conclusion: Taken together, our data demonstrate clearly that NUCKS1 is a novel Tat coactivator that is required for Tat-mediated HIV-1 transcription and replication, and that it may contribute to HIV-1 reactivation in latently HIV-1 infected cells.

Original languageEnglish
Article number67
JournalRetrovirology
Volume11
Issue number1
DOIs
StatePublished - 13 Aug 2014

Bibliographical note

Funding Information:
This work was supported by an intramural grant from the Korea National Institute of Health (Grant Number: 2013-N51002-00 and 2013-E51004-00).

Publisher Copyright:
© 2014 Kim et al.; licensee BioMed Central Ltd.

Keywords

  • HIV-1 Tat
  • HIV-1 transcription
  • LTR
  • NUCKS1
  • TAR-RNA

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