Phosphorylation of Human Polyomavirus Large and Small T Antigens: An Ignored Research Field

Abstract

Protein phosphorylation and dephosphorylation are the most common post-translational modifications mediated by protein kinases and protein phosphatases, respectively. These reversible processes can modulate the function of the target protein, such as its activity, subcellular localization, stability, and interaction with other proteins. Phosphorylation of viral proteins plays an important role in the life cycle of a virus. In this review, we highlight biological implications of the phosphorylation of the monkey polyomavirus SV40 large T and small t antigens, summarize our current knowledge of the phosphorylation of these proteins of human polyomaviruses, and conclude with gaps in the knowledge and a proposal for future research directions.

Keywords: Merkel cell polyomavirus; SV40; human polyomavirus; large T antigen; protein kinase; small t antigen.

Figure 1

Conserved putative phosphoacceptor sites in LTAg and sTAg of HPyV. (A) The LTAg of SV40 and HPyV with the number of amino acid residues in parenthesis. The conserved Hsc70 binding domain (DnaJ), retinoblastoma family members binding motif LXCEX (pRb), the nuclear localization signal (NLS) and the DNA binding domain (DBD) are depicted. The proven phosphorylation sites in SV40 are shown on top of LTAg. The conserved residues and their corresponding residues in the LTAg of HPyV are shown in red. (B) Conserved putative phosphoacceptor site in SV40 and HPyV sTAg. SV40 T156 is conserved in all HPyVs except JCPyV. The number of amino acids is shown in parenthesis. The conserved Hsc70 binding domain (DnaJ) is indicated. The Betapolyomaviruses are shown first because they are most closely related to SV40.

Figure 1

Conserved putative phosphoacceptor sites in LTAg and sTAg of HPyV. (A) The LTAg of SV40 and HPyV with the number of amino acid residues in parenthesis. The conserved Hsc70 binding domain (DnaJ), retinoblastoma family members binding motif LXCEX (pRb), the nuclear localization signal (NLS) and the DNA binding domain (DBD) are depicted. The proven phosphorylation sites in SV40 are shown on top of LTAg. The conserved residues and their corresponding residues in the LTAg of HPyV are shown in red. (B) Conserved putative phosphoacceptor site in SV40 and HPyV sTAg. SV40 T156 is conserved in all HPyVs except JCPyV. The number of amino acids is shown in parenthesis. The conserved Hsc70 binding domain (DnaJ) is indicated. The Betapolyomaviruses are shown first because they are most closely related to SV40.