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The cyclin-dependent kinase Cdk1 directly regulates vacuole inheritance.

ABSTRACT: In budding yeast, vacuole inheritance is tightly coordinated with the cell cycle. The movement of vacuoles and several other organelles is actin-based and is mediated by interaction between the yeast myosin V motor Myo2 and organelle-specific adaptors. Myo2 binds to vacuoles via the adaptor protein Vac17, which binds to the vacuole membrane protein Vac8. Here we show that the yeast cyclin-dependent kinase Cdk1 phosphorylates Vac17 and that phosphorylation of Vac17 parallels cell cycle-dependent movement of the vacuole. Substitution of the Cdk1 sites in Vac17 decreases its interaction with Myo2 and causes a partial defect in vacuole inheritance. This defect is enhanced in the presence of Myo2 with mutated phosphorylation sites. Thus, Cdk1 appears to control the timing of vacuole movement. The presence of multiple predicted Cdk1 sites in other organelle-specific myosin V adaptors suggests that the inheritance of other cytoplasmic organelles may be regulated by a similar mechanism.

SUBMITTER: Peng Y

PROVIDER: S-EPMC2727752 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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The cyclin-dependent kinase Cdk1 directly regulates vacuole inheritance.

Peng Yutian Y Weisman Lois S LS

Developmental cell 20080901 3

In budding yeast, vacuole inheritance is tightly coordinated with the cell cycle. The movement of vacuoles and several other organelles is actin-based and is mediated by interaction between the yeast myosin V motor Myo2 and organelle-specific adaptors. Myo2 binds to vacuoles via the adaptor protein Vac17, which binds to the vacuole membrane protein Vac8. Here we show that the yeast cyclin-dependent kinase Cdk1 phosphorylates Vac17 and that phosphorylation of Vac17 parallels cell cycle-dependent ...[more]

PMID: 18804442

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Project description:Simple Summary Cyclin-dependent kinase 1 (CDK1), one of the key regulators of the G2/M checkpoint, is expressed in many cells and plays an important role in cell cycle control. However, CDK1 expression is substantially increased in many tumors of diverse origins and is associated with tumorigenesis. Targeting CDK1 shows promising results for several tumors. However, a systematic and integrative analysis of CDK1 in cancer has not been conducted. The present study aims to use pan-cancer analysis to investigate the relationship, similarities, and differences in genetic and cellular changes associated with CDK1 in various tumors and tumor microenvironments. Our findings elucidate that CDK1 expression increases in more than 20 human tumors and is highly correlated with oncogenic signature gene sets, biological pathways, immune cell infiltration, tumor mutational burden, microsatellite instability, and lower survival rate across multiple tumors. Targeting CDK1 may provide a novel and effective strategy for cancer immunotherapy. Abstract Cyclin-dependent kinase 1 (CDK1) is essential for cell division by regulating the G2/M phase and mitosis. CDK1 overexpression can also promote the development and progression of a variety of cancers. However, the significance of CDK1 in the formation, progression, and prognosis of human pan-cancer remains unclear. In the present study, we used The Cancer Genome Atlas database, Clinical Proteomic Tumor Analysis Consortium, Human Protein Atlas, Genotype-Tissue Expression, and other well-established databases to comprehensively examine CDK1 genetic alterations and gene/protein expression in various cancers and their relationships with the prognosis, immune reactivities, and clinical outcomes for 33 tumor types. Gene set enrichment analysis was also conducted to examine the potential mechanisms of CDK1 in tumorigenesis. The data showed that CDK1 mutation was frequently present in multiple tumors. CDK1 expression was significantly increased in various types of tumors as compared with normal tissues and was associated with poor overall and disease-free survival. In addition, CDK1 expression was significantly correlated with oncogenic genes, proteins, cellular components, myeloid-derived suppressor cell infiltration, ESTMATEScore, and signaling pathways associated with tumor development and progression and tumor microenvironments. These data indicate that CDK1 could serve as a promising biomarker for predicting tumor prognosis and a potential target for cancer treatment.

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The cyclin-dependent kinase Cdk1 directly regulates vacuole inheritance.

Publications

The cyclin-dependent kinase Cdk1 directly regulates vacuole inheritance.

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