Tip110, the human immunodeficiency virus type 1 (HIV-1) Tat-interacting protein of 110 kDa as a negative regulator of androgen receptor (AR) transcriptional activation

Ying Liu, Byung Oh Kim, Chinghai Kao, Chaeyong Jung, James T. Dalton, Johnny J. He

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Upon binding to androgen, androgen receptor (AR) can activate expression of target genes through its direct binding to the androgen-responsive elements (AREs), which are located within the target gene promoters and/or enhancers. A number of cellular proteins have been identified as co-regulators to regulate this transactivation process. One common structural feature among these co-regulators is the presence of the LXXLL motif (X, any amino acid), the so-called nuclear receptor (NR) box, through which binding of these regulatory proteins to AR occurs. We have recently shown that Tip110 functions to potentiate the transactivation activity of human immunodeficiency virus type I (HIV-1) Tat protein. In this study, we report that Tip110 is a potent AR-binding protein that can suppress AR activity. Tip110 bound to AR in an NR box-dependent manner and inhibited AREs-mediated reporter gene expression. The inhibitory effects were abolished by removal of the NR box. Moreover, knock-down of the constitutive Tip110 expression significantly augmented AR transcriptional activation. In agreement with these findings, Tip110 overexpression blocked the prostate-specific antigen (PSA) gene, a well characterized target gene of AR from expression in LNCaP cells. Further analysis revealed that Tip110 prevented the complex formation between AR and AREs. Taken together, these results indicate that Tip110 is a negative regulator of AR transcriptional activation, and may be directly involved in AR-related developmental, physiological, and pathological processes.

Original languageEnglish
Pages (from-to)21766-21773
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number21
DOIs
StatePublished - May 21 2004

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tat Gene Products
Androgen Receptors
Viruses
Transcriptional Activation
HIV-1
Chemical activation
Proteins
Androgens
Cytoplasmic and Nuclear Receptors
Genes
Androgen-Binding Protein
Physiological Phenomena
Gene Expression
Pathologic Processes
Prostate-Specific Antigen
Reporter Genes
Gene expression
Carrier Proteins
HIV

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tip110, the human immunodeficiency virus type 1 (HIV-1) Tat-interacting protein of 110 kDa as a negative regulator of androgen receptor (AR) transcriptional activation. / Liu, Ying; Kim, Byung Oh; Kao, Chinghai; Jung, Chaeyong; Dalton, James T.; He, Johnny J.

In: Journal of Biological Chemistry, Vol. 279, No. 21, 21.05.2004, p. 21766-21773.

Research output: Contribution to journalArticle

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