Animal models for studying the in vivo functions of cell cycle CDKs

Sanjiv Risal, Deepak Adhikari, Kui Liu

Research output: Contribution to journalArticleOtherpeer-review

Abstract

Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.

Original languageEnglish
Pages (from-to)155-166
Number of pages12
JournalMethods in Molecular Biology
Volume1336
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • Cdk1
  • Cdk2
  • Cdk4
  • Cdk6
  • Cell cycle
  • Cyclin-dependent kinases
  • Cyclins
  • Mitosis

Cite this

@article{505e98516d69431ba7527bd4edae5c48,
title = "Animal models for studying the in vivo functions of cell cycle CDKs",
abstract = "Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.",
keywords = "Cdk1, Cdk2, Cdk4, Cdk6, Cell cycle, Cyclin-dependent kinases, Cyclins, Mitosis",
author = "Sanjiv Risal and Deepak Adhikari and Kui Liu",
year = "2016",
doi = "10.1007/978-1-4939-2926-9_13",
language = "English",
volume = "1336",
pages = "155--166",
journal = "Methods in Molecular Biology",
issn = "1064-3745",
publisher = "Humana Press",

}

Animal models for studying the in vivo functions of cell cycle CDKs. / Risal, Sanjiv; Adhikari, Deepak; Liu, Kui.

In: Methods in Molecular Biology, Vol. 1336, 2016, p. 155-166.

Research output: Contribution to journalArticleOtherpeer-review

TY - JOUR

T1 - Animal models for studying the in vivo functions of cell cycle CDKs

AU - Risal, Sanjiv

AU - Adhikari, Deepak

AU - Liu, Kui

PY - 2016

Y1 - 2016

N2 - Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.

AB - Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.

KW - Cdk1

KW - Cdk2

KW - Cdk4

KW - Cdk6

KW - Cell cycle

KW - Cyclin-dependent kinases

KW - Cyclins

KW - Mitosis

UR - http://www.scopus.com/inward/record.url?scp=84938632529&partnerID=8YFLogxK

U2 - 10.1007/978-1-4939-2926-9_13

DO - 10.1007/978-1-4939-2926-9_13

M3 - Article

VL - 1336

SP - 155

EP - 166

JO - Methods in Molecular Biology

JF - Methods in Molecular Biology

SN - 1064-3745

ER -