Human immunodeficiency virus-1 Tat protein interacts with distinct proteasomal α and β subunits

• Published in: FEBS letters 2003-10, Vol.553 (1), p.200-204
• Main Authors: Apcher, G.Sébastien, Heink, Sylvia, Zantopf, Daniela, Kloetzel, Peter-M., Schmid, Hans-P., Mayer, R.John, Krüger, Elke
• Format: Article
• Language: English
• Subjects: Antigen presentation; Cell Line; Cysteine Endopeptidases - chemistry; Cysteine Endopeptidases - metabolism; Cysteine Proteinase Inhibitors - metabolism; Gene Products, tat - metabolism; GFP, green fluorescent protein; GSH, glutathione; GST, glutathione S-transferase; HeLa Cells; HIV-1, human immunodeficiency virus-1; Human immunodeficiency virus; Humans; IFNγ, interferon-γ; Major histocompatibility complex class I; MHC, major histocompatibility complex; Multienzyme Complexes - chemistry; Multienzyme Complexes - metabolism; Precipitin Tests; Proteasome; Proteasome Endopeptidase Complex; Proteasome inhibition; Protein Binding; Protein Subunits - chemistry; Protein Subunits - metabolism; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(03)01025-1

The human immunodeficiency virus-1 (HIV-1) Tat protein was previously reported to compete the association of PA28 regulator with the α rings of the 20S proteasome and to inhibit its peptidase activity. However, the distinct interaction sites within the proteasome complex remained to be determined. Here we show that HIV-1 Tat binds to α4 and α7, six β subunits of the constitutive 20S proteasome and the interferon-γ-inducible subunits β2i and β5i. A Tat–proteasome interaction can also be demonstrated in vivo and leads to inhibition of proteasomal activity. This indicates that Tat can modulate or interfere with cellular proteasome function by specific interaction with distinct proteasomal subunits.