RESUMO
Cyclin-dependent kinase 6 (Cdk6) is a D-Cyclin-activated kinase that is directly involved in driving the cell cycle through inactivation of pRB in G1 phase. Increasingly, evidence suggests that CDK6, while directly driving the cell cycle, may only be essential for proliferation of specialized cell types, agreeing with the notion that CDK6 also plays an important role in differentiation. Here, evidence is presented that CDK6 binds to and promotes degradation of the EYA2 protein. The EYA proteins are a family of proteins that activate genes essential for the development of multiple organs, regulate cell proliferation, and are misregulated in several types of cancer. This interaction suggests that CDK6 regulates EYA2 activity, a mechanism that could be important in development and in cancer.
Assuntos
Quinase 6 Dependente de Ciclina/metabolismo , Fase G1/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Proteólise , Ciclo Celular/genética , Diferenciação Celular/genética , Proliferação de Células , Quinase 6 Dependente de Ciclina/genética , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Tirosina Fosfatases/genéticaRESUMO
Several studies have recently reported that the cyclin dependent kinase (cdk) 6 oncogene plays a role in differentiation of a variety of cell types. This novel function expands the previously understood function of cdk6 as a regulator of G(1) phase of the cell cycle. The proposed mechanisms of these functions both require nuclear localization. That is, cdk6 phosphorylation of the retinoblastoma protein (pRb) to regulate cell cycle, and the recently proposed transcriptional regulation to block differentiation, are both nuclear functions that predict nuclear localization of the kinase. This report provides a thorough analysis of cdk6 localization and compares the localization of a commonly used mutant cdk6 to the corrected wildtype sequence as recorded in GenBank. The widely shared mutant of cdk6 contains a tyrosine residue at amino acid 224 (instead of an aspartic acid) introducing a potential phosphorylation site to the cdk6 sequence. Results indicate a majority of cdk6 is localized to the cytoplasm with concentrations of cdk6 in the edges of the cytoplasm and in the cytoplasmic extensions of cells. The results of this study may help to better understand the emerging roles of cdk6 in cell cycle control, differentiation and cancer.
