ATP1B3 Protein Modulates the Restriction of HIV-1 Production and Nuclear Factor κ Light Chain Enhancer of Activated B Cells (NF-κB) Activation by BST-2

J Biol Chem. 2016 Feb 26;291(9):4754-62. doi: 10.1074/jbc.M115.679357. Epub 2015 Dec 22.

Abstract

Here, we identify ATP1B3 and fibrillin-1 as novel BST-2-binding proteins. ATP1B3 depletion in HeLa cells (BST-2-positive cells), but not 293T cells (BST-2-negative cells), induced the restriction of HIV-1 production in a BST-2-dependent manner. In contrast, fibrillin-1 knockdown reduced HIV-1 production in 293T and HeLa cells in a BST-2-independent manner. Moreover, NF-κB activation was enhanced by siATP1B3 treatment in HIV-1- and HIV-1ΔVpu-infected HeLa cells. In addition, ATP1B3 silencing induced high level BST-2 expression on the surface of HeLa cells. These results indicate that ATP1B3 is a co-factor that accelerates BST-2 degradation and reduces BST-2-mediated restriction of HIV-1 production and NF-κB activation.

Keywords: ATP1B3; BST-2; NF-kappa B (NF-KB); Na+/K+-ATPase; bone marrow; cell biology; cell surface protein; human immunodeficiency virus (HIV); membrane trafficking; retrovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / chemistry
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cell Line
  • Fibrillin-1
  • Fibrillins
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / chemistry
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Deletion
  • Gene Expression Regulation
  • HEK293 Cells
  • HIV-1 / physiology*
  • HeLa Cells
  • Humans
  • Microfilament Proteins / antagonists & inhibitors
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • NF-kappa B / agonists
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Protein Interaction Domains and Motifs
  • Protein Stability
  • Proteolysis
  • RNA Interference
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / chemistry
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Two-Hybrid System Techniques
  • Viral Tropism
  • Virus Replication

Substances

  • ATP1B3 protein, human
  • Antigens, CD
  • BST2 protein, human
  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • GPI-Linked Proteins
  • Microfilament Proteins
  • NF-kappa B
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Sodium-Potassium-Exchanging ATPase