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Thymidine kinase 1 regulatory fine-tuning through tetramer formation.

In English

Författare

  • Zeeshan Mutahir
  • Anders Ranegaard Clausen
  • Karl-Magnus Andersson
  • Sofia Mebrahtu Wisén
  • Birgitte Munch-Petersen
  • Jure Piskur

Summary, in English

Thymidine kinase 1 (TK1) provides a crucial precursor, thymidine monophosphate (dTMP), for nucleic acid synthesis, and the activity of TK1 increases up to 200-fold during the S-phase of cell division in humans. An important part of the regulatory check-points is the ATP and enzyme concentration-dependent transition of TK1 from a dimer with low catalytic efficiency to a tetramer with high catalytic efficiency. This regulatory fine-tuning serves as an additional control to provide the balanced pool of nucleic acid precursors in the cell. We sub-cloned and over-expressed ten different TK1s, originating from widely different organisms, and characterized their kinetic and oligomerization properties. While bacteria, plants and Dictyostelium only exhibited dimeric TK1, we found that all animals had a tetrameric TK1. However, a clear ATP dependent switch between dimer and tetramer was found only in higher vertebrates, and was especially pronounced in mammalian and bird TK1s. We suggest that the dimer form is the original one and the tetramer originated in the animal lineage after the split of Dictyostelium and the lineages leading to invertebrates and vertebrates. The efficient switching mechanism was likely settled first in the warm-blooded animals when they separated from the rest of vertebrates. © 2013 The Authors Journal compilation © 2013 FEBS.

Publiceringsår

2013

Språk

Engelska

Sidor

1531-1541

Publikation/Tidskrift/Serie

The FEBS Journal

Volym

280

Issue

6

Dokumenttyp

Artikel i tidskrift

Förlag

Wiley-Blackwell

Ämne

  • Biological Sciences

Nyckelord

  • Thymidine kinase 1
  • Regulatory switch
  • Evolution of enzyme regulation
  • Oligomerization

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1742-464X