Small tumor antigen

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The small tumor antigen (also called the small T-antigen and abbreviated STag or ST) is a

oncoprotein in its own right.[3]

Structure and expression

WU virus, a typical human polyomavirus. The early genes are at left, comprising LTag (purple) and STag (blue); the late genes are at right, and the origin of replication is shown at the top of the figure.[4]

The genes for both the small and the

molecular chaperone.[2][7]

The C-terminal portion of the STag protein is distinct from LTag but shares an additional ~100 residues with

genus Gammapolyomavirus - the conserved cysteines characterizing these metal-binding regions are not present and there is no detectable sequence homology between the avian and mammalian STag C-termini.[11]

Function

The exact functional role of STag varies among polyomaviruses. In

oncogenesis, a function performed primarily by LTag in other polyomaviruses.[3] Where the tumor antigens' subcellular localization has been characterized, STag is usually located in the cytoplasm.[8]

Viral replication

In most well-studied polyomaviruses, STag improves the efficiency of viral proliferation but is not

Hsc70 to increase its ATPase activity.[2]

Effects on the cell cycle

The SV40 polyomavirus small tumor antigen (STag) J domain (yellow) and unique region (blue) in complex with the human protein phosphatase 2A (PP2A) A subunit (red).[1]
The human protein phosphatase 2A (PP2A) heterotrimeric complex, shown with the regulatory subunit A (red), regulatory subunit B56 (green), and catalytic subunit (dark blue).[12] The overlap between the STag and B56 binding sites on the A subunit is clear.

Because polyomavirus genome replication relies on the DNA replication machinery of the host cell, the cell must be in S phase (the part of the cell cycle in which the host cell's genome is normally replicated) in order to provide the necessary molecular machinery for viral DNA replication. Viral proteins therefore promote dysregulation of the cell cycle and entry into S phase. This function is usually primarily provided by LTag through its interactions with retinoblastoma protein and p53.[7][13]

STag contributes to this process through its interaction with protein phosphatase 2A (PP2A).[14] The active form of PP2A consists of a heterotrimer assembly of three subunits. X-ray crystallography of the STag-PP2A protein complex demonstrates that STag replaces one subunit in the complex, thereby inactivating it.[2][1][15][16]

Cellular transformation

Some, but not all, polyomaviruses are

neoplastic transformation in some cells. In oncogenic polyomaviruses, the tumor antigens are responsible for the transformation activity, although the exact molecular mechanisms vary from one virus to another.[13][7][17] STag is usually not capable of inducing these effects on its own, but increases efficiency of transformation or is sometimes a required component in addition to LTag.[2] In most polyomaviruses, STag's effect on transformation is mediated through its interaction with PP2A.[16]

Distinct functions in Merkel cell polyomavirus

animal models suggest that MCPyV STag alone can be sufficient to drive transformation.[20]

References

  1. ^
    PMID 17608567
    .
  2. ^
    PMID 18022798
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  3. ^
    PMID 26608318
    .
  4. PMID 17480120
    .
  5. S2CID 31314244
    .
  6. PMID 22461085
    .
  7. ^
    PMID 23201316
    .
  8. ^
    PMID 19505649
    .
  9. PMID 8388518
    .
  10. PMID 1310775
    .
  11. PMID 27093155
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  12. S2CID 4408160
    .
  13. ^
    PMID 22994493
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  14. S2CID 2007706
    .
  15. S2CID 82822
    .
  16. ^
    S2CID 7715684
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  17. PMID 24978434
    .
  18. PMID 25681708
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  19. PMID 21841310
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  20. PMID 25313532
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