Cell and Tissue Research

, Volume 336, Issue 3, pp 521–527

Nuclear transport of protein TTC4 depends on the cell cycle

  • Ruslan I. Dmitriev
  • Irina A. Okkelman
  • Roman A. Abdulin
  • Mikhail I. Shakhparonov
  • Nikolay B. Pestov
Short Communication


TTC4 (tetratricopeptide repeat domain protein 4) is a putative tumor suppressor involved in the transformation of melanocytes. At present, the relationships between TTC4 and DNA replication proteins are largely unknown, as are the tissue distribution and subcellular localization of TTC4. Using reverse transcription with the polymerase chain reaction, we have observed that the murine TTC4 gene is ubiquitously expressed. Analysis of the TTC4 subcellular localization has shown that, upon overexpression, TTC4 localizes to the cytoplasm. Interestingly, co-expression with a known protein interaction partner, hampin/MSL1, results in the nuclear translocation of the TTC4 protein. The subcellular localization of endogenous TTC4 depends, however, on the cell cycle: it is mostly nuclear in the G1 and S phases and is evenly distributed between the nucleus and cytoplasm in G2. The nuclear transport of TTC4 is apparently a complex process dependent on interactions with other proteins during the progression of the cell cycle. Thus, the dynamic character of the nuclear accumulation of TTC4 might be a potential link with regard to its function in tumor suppression.


TTC4 Hampin Cell cycle Mouse TPR 

Supplementary material

441_2009_785_Fig1_ESM.gif (201 kb)
Figure S1

Heterogeneity of subcellular location of endogenous TTC4 protein in asynchronous fibroblasts. Sections 1 and 3 show a typical cell with predominantly nuclear TTC4, whereas in sections 2, 4 another cell from the same culture has TTC4 evenly distributed between its nucleus and cytoplasm. 3T3 cells were fixed in cold methanol and stained with anti-TTC4 antibodies followed by Alexa Fluor 488-conjugated anti-rabbit antibodies (green fluorescence) and counterstained with DAPI (blue fluorescence). 1,2 - green channel, 3,4 - merge. Bar, 50 μm. (GIF 200 KB)

441_2009_785_Fig1_ESM.tif (5.5 mb)
High resolution image file (TIF 8.3 MB)
441_2009_785_Fig2_ESM.gif (75 kb)
Figure S2

Effect of the cell cycle on subcellular distribution of the protein TTC4. 3T3 fibroblasts were synchronized by serum starvation and subsequently incubated with serum for specified time before fixation in cold methanol and staining with anti-TTC4 antibodies. Green fluorescence - Alexa Fluor 488-conjugated anti-rabbit antibodies (TTC4), blue fluorescence in left row - DAPI (nuclei). From top to bottom: 0, 7, 10, 14 and 22 hrs incubations with serum. Bar, 50 μm. (GIF 74.9 KB)

441_2009_785_Fig2_ESM.tif (19.9 mb)
High resolution image file (TIF 19.8 MB)
441_2009_785_Fig3_ESM.gif (72 kb)
Figure S3

Absence of effect of CRM1-nuclear export inhibitor LMB on TTC4 subcellular location. Hela cells were transfected by TTC4-encoding plasmid DNAs GFP-TTC4 or TTC4-RFP and treated by 100 nM LMB for 20 min. Live cells were imaged before and after treatment. 1 - TTC4-RFP before LMB treatment; 2 - TTC4-RFP after treatment; 3 - GFP-TTC4 before treatment; 4 - GFP-TTC4 after treatment. Bar, 50 μm. (GIF 72.2 KB)

441_2009_785_Fig3_ESM.tif (7.2 mb)
High resolution image file (TIF 12.8 MB)


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ruslan I. Dmitriev
    • 1
  • Irina A. Okkelman
    • 1
  • Roman A. Abdulin
    • 1
  • Mikhail I. Shakhparonov
    • 1
  • Nikolay B. Pestov
    • 1
  1. 1.Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesMoscowRussia

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