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  • Original Paper
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Characterization of VIK-1: a new Vav-interacting Kruppel-like protein

Oncogene volume 24, pages 28–38 (2005)Cite this article

Abstract

Binding partners of the Src homology domains of Vav-1 were characterized by a two-hybrid screening of a Jurkat cell cDNA library. One of the isolated clones encoded a new protein named VIK that belongs to the Kruppel-like zinc-finger gene family. Genome mapping showed that a single gene positioned at chromosome 7q22.1 generated three possible isoforms containing alternative domains such as proline-rich and Kruppel-associated box A or B repressor domains. The isolated isoform, VIK-1, did not contain such motifs but presented six tandemly arranged zinc-fingers and consensus Kruppel H–C links. VIK-1 interacted both with Vav-1 and cyclin-dependent kinase 4 through two independent domains and corresponded to a Vav C-Src homology domain (SH)3 partner able to shuttle between the nucleus and the cytoplasm exhibiting functional nuclear addressing and export sequences. The results indicated a restricted expression of the protein during the G1 phase and its overexpression resulted in an inhibition of the cell-cycle progression that was reversed in the presence of Vav 1. Thus, this ubiquitous factor provides a first link between Vav-1 and the cell-cycle machinery.

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Abbreviations

GFP:

green fluorescent protein

FITC:

fluorescein isothiocyanate

PMA:

phorbol 12-myristate 13-acetate

NLS:

nuclear localization sequence

NES:

nuclear export sequence

KLF:

Kruppel-like factor

SH:

Src homology domain

KRAB:

Kruppel-associated box

CDK4:

cyclin-dependent kinase 4

GST:

glutathione S-transferase

aa:

amino acid

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Acknowledgements

We thank Dr C Sardet for providing CDK4 constructs. We are also grateful to F Heutte, F Letourneur, MC Gendron, B Channaud and L Touvenel for technical assistance in various technologies. This work was supported by grants from the Association pour la Recherche contre le Cancer and La Ligue Nationale contre le Cancer. MH and AD are recipients of grants from La Fondation pour la Recherche Médicale and Ministère de la Recherche et de la Technologie, respectively. The sequence reported in this paper has been submitted to the GenBankTM/EBI Data Bank with Accession number AY099353.

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Author notes

  1. Martin Houlard: SBGM, Laboratoire de transgénèse, CEA Saclay, Gif sur Yvette 91191, France

  2. Francisco Romero-Portillo: Departamento de microbiologia, Faculdad de Biologia, Apdo. 1095, Sevilla 4108, Spain

  3. Antonia Germani: Laboratorio di patologia vascolare, IDI, Via Monti di Creta 104, Roma 00167, Italy

Authors and Affiliations

  1. Département d'Hématologie, Institut Cochin, Hôpital Cochin, 27, rue du Faubourg Saint Jacques, Paris, 75014, France

    Martin Houlard, Francisco Romero-Portillo, Antonia Germani, Arnaud Depaux, Fabienne Regnier-Ricard, Sylvie Gisselbrecht & Nadine Varin-Blank

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Correspondence to Nadine Varin-Blank.

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Houlard, M., Romero-Portillo, F., Germani, A. et al. Characterization of VIK-1: a new Vav-interacting Kruppel-like protein. Oncogene 24, 28–38 (2005). https://doi.org/10.1038/sj.onc.1208043

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