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Identification of a putative human mitochondrial thymidine monophosphate kinase associated with monocytic/macrophage terminal differentiation.

Authors
  • Chen, Yen-Ling
  • Lin, Da-Wei
  • Chang, Zee-Fen
Type
Published Article
Journal
Genes to Cells
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jul 01, 2008
Volume
13
Issue
7
Pages
679–689
Identifiers
DOI: 10.1111/j.1365-2443.2008.01197.x
PMID: 18498354
Source
Medline
License
Unknown

Abstract

Mitochondrial DNA synthesis requires the supply of thymidine triphosphate (dTTP) independent of nuclear DNA replication. In resting and differentiating cells that withdraw from the cell cycle, mitochondrial thymidine kinase 2 (TK2) mediates thymidine monophosphate (dTMP) formation for the dTTP biosynthesis in mitochondria. However, a thymidine monophosphate kinase (TMPK) that phosphorylates dTMP to form thymidine diphosphate (dTDP) in mitochondria remains undefined. Here, we identified an expressed sequence tag cDNA, which encodes a TMPK with a mitochondrial import sequence at its N-terminus designated as TMPK2. HeLa cells expressing TMPK2 fused to green fluorescent protein (GFP) displayed green fluorescence in mitochondria. Over-expression of TMPK2 increased the steady-state level of cellular dTTP and promoted the conversion of radioactive labeled-thymidine and -dTMP to dTDP and dTTP in mitochondria. TMPK2 RNA was detected in several tissues and erythroblastoma cell lines. We also generated TMPK2 antibody and used it for immunofluorescence staining to demonstrate endogenous expression of TMPK2 in mitochondria of erythroblastoma cells. Finally, we showed that TMPK2 protein expression was upregulated in monocyte/macrophage differentiating cells, suggesting the coordinated regulation of TMPK2 expression with the terminal differentiation program.

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