Surface expressed nucleolin is constantly induced in tumor cells to mediate calcium-dependent ligand internalization.

Background: Nucleolin is one of the major proteins of the nucleolus, but it is also expressed on the cell surface where is serves as a binding protein for variety of ligands implicated in tumorigenesis and angiogenesis. Emerging evidence suggests that the cell-surface expressed nucleolin is a strategic target for an effective and nontoxic cancer therapy.

Methodology/principal Findings: By monitoring the expression of nucleolin mRNA, and by measuring the level of nucleolin protein recovered from the surface and nucleus of cells, here we show that the presence of nucleolin at the cell surface is dependent on the constant induction of nucleolin mRNA.

HIV-1 neutralizing antibodies elicited by the candidate CBD1 epitope vaccine react with the conserved caveolin-1 binding motif of viral glycoprotein gp41.

To date, candidate HIV-1 vaccines that have been tested in clinical trials have failed to induce broadly neutralizing activities and/or antibodies that inhibit infection by primary isolates of HIV-1. We recently identified a conserved caveolin-1 binding motif, WNNMTWMQW, in the ectodomain of HIV-1 transmembrane envelope glycoprotein gp41. We designed the synthetic CBD1 peptide SLEQIWNNMTWMQWDK, corresponding to the consensus caveolin-1 binding domain (CBD) in gp41, and showed that it elicits in rabbits the production of antibodies that inhibit infection of primary CD4(+) T lymphocytes by various primary HIV-1 isolates.

Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin.

The growth factor pleiotrophin (PTN) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles to cells. Here we show that PTN inhibits HIV-1 infection by its capacity to inhibit HIV-1 particle attachment to the surface of permissive cells. The beta-sheet domains of PTN appear to be implicated in this inhibitory effect on the HIV infection, in particular the domain containing amino acids 60-110.

The caveolin-1 binding domain of HIV-1 glycoprotein gp41 is an efficient B cell epitope vaccine candidate against virus infection.

Caveolin-1 is a scaffolding protein that organizes and concentrates specific ligands within the caveolae membranes. We identified a conserved caveolin-1 binding motif in the HIV-1 transmembrane envelope glycoprotein gp41 and designed several synthetic peptides, referred to as CBD1, corresponding to the consensus caveolin-1 binding domain in gp41. In rabbits, these peptides elicit the production of antibodies that inhibit infection of primary CD4(+) T lymphocytes by various primary HIV-1 isolates.

The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor.

The growth factor midkine (MK) is a cytokine that inhibits the attachment of human immunodeficiency virus particles by a mechanism similar to the nucleolin binding HB-19 pseudopeptide. Here we show that the binding of MK to cells occurs specifically at a high and a low affinity binding site. HB-19 prevents the binding of MK to the low affinity binding site only.