Unknown

Dataset Information

0

A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis.

ABSTRACT: Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. To determine the role of CDK6 in development and tumorigenesis, we generated and analyzed knockout mice. Cdk6-deficient mice show pronounced thymic atrophy due to reduced proliferative fractions and concomitant transitional blocks in the double-negative stages. Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. Furthermore, CDK6-deficient mice were resistant to lymphomagenesis induced by active Akt, a downstream target of Notch signaling. These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies.

SUBMITTER: Hu MG 

PROVIDER: S-EPMC2636510 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. To determine the role of CDK6 in development and tumorigenesis, we generated and analyzed knockout mice. Cdk6-deficient mice show pronounced thymic atrophy due to reduced proliferative fractions and concomitant transitional blocks in the double-negative stages. Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is requi  ...[more]

Similar Datasets

Unknown Cyclin D2-cyclin-dependent kinase 4/6 is required for efficient proliferation and tumorigenesis following Apc loss.
| S-EPMC2974087 | biostudies-literature
Unknown Cyclin-dependent kinase 5 is required for normal cerebellar development.
| S-EPMC3540197 | biostudies-literature
Unknown Unexpected reduction of skin tumorigenesis on expression of cyclin-dependent kinase 6 in mouse epidermis.
| S-EPMC3069882 | biostudies-literature
Unknown An unliganded thyroid hormone beta receptor activates the cyclin D1/cyclin-dependent kinase/retinoblastoma/E2F pathway and induces pituitary tumorigenesis.
| S-EPMC538780 | biostudies-literature
Unknown The Indispensable Role of Cyclin-Dependent Kinase 1 in Skeletal Development.
| S-EPMC4816159 | biostudies-literature
Unknown CDK6 kinase activity is required for thymocyte development.
| S-EPMC3122937 | biostudies-literature
Unknown Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance.
| S-EPMC3817326 | biostudies-literature
Unknown Presenilin-dependent gamma-secretase activity modulates thymocyte development.
| S-EPMC55417 | biostudies-literature
Unknown Requirement for A-type cyclin-dependent kinase and cyclins for the terminal division in the stomatal lineage of Arabidopsis.
| S-EPMC4036514 | biostudies-literature
Unknown The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity.
| S-EPMC2875168 | biostudies-literature