Characterization of VIK-1: a new Vav-interacting Kruppel-like protein.
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.
Houlard
Martin
M
Département d'Hématologie, Institut Cochin, Hôpital Cochin 27, rue du Faubourg Saint Jacques, Paris 75014, France.
Romero-Portillo
Francisco
F
Germani
Antonia
A
Depaux
Arnaud
A
Regnier-Ricard
Fabienne
F
Gisselbrecht
Sylvie
S
Varin-Blank
Nadine
N
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D051741:Kruppel-Like Transcription Factors; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav
D002352:Carrier Proteins; D005656:Fungal Proteins; D051741:Kruppel-Like Transcription Factors; D008869:Microtubule-Associated Proteins; D019913:Nuclear Localization Signals; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; C119241:VIK1 protein, S cerevisiae; C496408:ZNF655 protein, human; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases