Non-Cell Cycle Functions of Cell Cycle Regulators

Editorial

27 June 2019

Editorial: Non-cell Cycle Functions of Cell Cycle Regulators

Song-Tao Liu

Gordon K. Chan

and

Weimin Li

5,556 views

4 citations

Editors

Song-Tao Liu

University of Toledo

Gordon Chan

Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta

Weimin Li

Washington State University

Impact

Review

26 February 2019

Immunomodulatory Roles of Cell Cycle Regulators

Phatthamon Laphanuwat

and

Siwanon Jirawatnotai

Core cell cycle regulators, including cyclin-dependent kinases (CDKs), cyclins, and cyclin-dependent kinase inhibitors (CKIs), are known for their well-characterized roles in cell division. Several recent studies have shed light on the roles of these proteins in immune modulation. The development and activation of cells in the immune system take place not only during embryonic development but throughout the life of a multicellular organism. Cell cycle regulators are involved in the development of immune cells, partly as the machinery controlling the expansion and differentiation of the populations of immune cells. In addition, these proteins serve non-cell cycle functions. In this review, we summarize the emerging roles of cell cycle regulators in modulating functions of the immune system and discuss how they may be exploited as therapeutic targets.

8,992 views

59 citations

Subcellular localization of p27. (A,B,E–K) Primary cortical neurons from E15 cerebral cortices incubated for 2 days in vitro and stained with the indicated antibodies. Immunocytochemical analyses were performed as described previously (Shikanai et al., 2018a). Fluorescence images were obtained by A1R laser scanning confocal microscopy with a high sensitivity GaAsP detector (Nikon) using the narrow pinhole size (0.3) and subjected to deconvolution processing with the Richardson-Lucy algorithm in NIS-ER software (Nikon). The graph in (K) shows the colocalization efficient (Pearson’s correlation) of the indicated proteins with p27, as determined using NIS elements software (Nikon). Significance was determined by Kruskal-Wallis test with post hoc Steel-Dwass test [< the critical value at 1% (Rab6 vs. SNX6 or LAMTOR1 or Rab5 or Rab7 or Rab8 or Rab11 or β-tubulin; p115 vs. SNX6 or LAMTOR1 or Rab5 or Rab7 or Rab8 or Rab11 or β-tubulin; GM130 vs. SNX6 or LAMTOR1 or Rab5 or Rab7 or Rab8 or Rab11 or β-tubulin. Dcx vs. SNX6 or LAMTOR1 or Rab5 or Rab7 or Rab8 or Rab11 or β-tubulin; Rab5 vs. LAMTOR1 or Rab7; LAMTOR1 vs. Rab8 or Rab11 or β-tubulin)]. (C,D) Primary cortical neurons from E15 cerebral cortices transfected with control vector or shRNA-expressing vector targeting for Rab7 (Rab7-sh108 (Kawauchi et al., 2010)) plus pCAG-EGFP (Kawauchi et al., 2003) and incubated for 2 days in vitro. Immunoblot analyses were performed as described previously (Kawauchi et al., 2006). The graph in (D) shows the ratios of immunoblot band intensities of p27/β-actin ± s.e.m. (n = 6). No significant differences (n.s.) between control and Rab7-sh108-transfected neurons were found by Student’s t-test (P = 0.3232). Primary antibodies used in this figure were anti-p27 (610241, BD Biosciences) (green in A,B,E,F,J, and immunoblots in C,D), anti-p27 (3686, Cell Signaling Technology) (red in G–I), anti-SNX6 (PA5-61948, Thermo Fisher Scientific), anti-LAMTOR1 (8975, Cell Signaling Technology), anti-Rab5 (3547, Cell Signaling Technology), anti-Rab6 (9625, Cell Signaling Technology), anti-Rab7 (9367, Cell Signaling Technology), anti-Rab8 (6975, Cell Signaling Technology), anti-Rab11 (5589, Cell Signaling Technology), anti-GM130 (610822, BD Biosciences), anti-p115 (612260, BD Biosciences), anti-β-tubulin (T5201, Sigma), anti-Dcx (4604, Cell Signaling Technology) and anti-β-actin (A5441, Sigma) antibodies. Scale bars: 4 μm in (E and upper panels in A,B,F), 1 μm in (lower panels in A,B, middle and lower panels in F), 1 μm in (G–J).

Perspective

26 April 2019

Growth Arrest Triggers Extra-Cell Cycle Regulatory Function in Neurons: Possible Involvement of p27kip1 in Membrane Trafficking as Well as Cytoskeletal Regulation

Takeshi Kawauchi

and

Yo-ichi Nabeshima

4,233 views

5 citations

Mini Review

14 January 2019

Molecular and in vivo Functions of the CDK8 and CDK19 Kinase Modules

Marius Volker Dannappel

, 2 more and

Ron Firestein

CDK8 and its paralog, CDK19, collectively termed ‘Mediator Kinase,’ are cyclin-dependent kinases that have been implicated as key rheostats in cellular homeostasis and developmental programming. CDK8 and CDK19 are incorporated, in a mutually exclusive manner, as part of a 4-protein complex called the Mediator kinase module. This module reversibly associates with the Mediator, a 26 subunit protein complex that regulates RNA Polymerase II mediated gene expression. As part of this complex, the Mediator kinases have been implicated in diverse process such as developmental signaling, metabolic homeostasis and in innate immunity. In recent years, dysregulation of Mediator kinase module proteins, including CDK8/19, has been implicated in the development of different human diseases, and in particular cancer. This has led to intense efforts to understand how CDK8/19 regulate diverse biological outputs and develop Mediator kinase inhibitors that can be exploited therapeutically. Herein, we review both context and function of the Mediator kinases at a molecular, cellular and animal level. In so doing, we illuminate emerging concepts underpinning Mediator kinase biology and highlight certain aspects that remain unsolved.

16,161 views

68 citations

Mini Review

17 August 2018

Fueling the Cycle: CDKs in Carbon and Energy Metabolism

Maria Solaki

and

Jennifer C. Ewald

Cyclin-dependent kinases (CDKs) are the central regulators of the eukaryotic cell cycle, and are conserved across eukaryotes. Their main and well-studied function lies in the regulation and the time-keeping of cell cycle entry and progression. Additionally, more and more non canonical functions of CDKs are being uncovered. One fairly recently discovered role of CDKs is the coordination of carbon and energy metabolism with proliferation. Evidence from different model organisms is accumulating that CDKs can directly and indirectly control fluxes through metabolism, for example by phosphorylating metabolic enzymes. In this mini-review, we summarize the emerging role of CDKs in regulating carbon and energy metabolism and discuss examples in different models from yeast to cancer cells.

6,554 views

43 citations