c-Rel in Epidermal Homeostasis: A Spotlight on c-Rel in Cell Cycle Regulation  Verena N. Lorenz, Michael P. Schön, Cornelia S. Seitz  Journal of Investigative Dermatology  Volume 136, Issue 6, Pages 1090-1096 (June 2016) DOI: 10.1016/j.jid.2016.02.003 Copyright © 2016 The Authors Terms and Conditions

Figure 1 Multiple functions of c-Rel in various organs and cell types. (a) Summarized functions of c-Rel in different organs and immune cells (B and T cells). The emerging pleiotropic activity of c-Rel includes functions in many central organ systems. (b) Control and c-Rel small interfering RNA-transfected HaCaT cells were stained for ß-tubulin (green). DAPI (blue) was used to counterstain DNA (images digitally enhanced). Control cells show normal bipolar spindle morphology around condensed chromatin, whereas mitotic cells with silenced c-Rel often show aberrantly centered, radial spindle morphology classified as monopolar. Size bars = 10 μm. ctrl, control; DAPI, 4′,6-diamidino-2-phenylindole. Journal of Investigative Dermatology 2016 136, 1090-1096DOI: (10.1016/j.jid.2016.02.003) Copyright © 2016 The Authors Terms and Conditions

Figure 2 The sequence of mitotic phases and associated spindle assembly checkpoint regulation. (a) The phases of mitosis (top row) have been visualized by immunofluorescence microscopy of HaCaT cells (spontaneously immortalized human keratinocytes) stained for ß-tubulin (mitotic spindle, green), pericentrin (centrosomes, red), and DNA (DAPI, blue). The schematic figures (bottom row) show the respective mitotic phases with the same color code. During prophase/prometaphase, centrosomes separate, move, and build up the bipolar mitotic spindle. After full chromosome condensation, the nuclear envelope dissolves. Starting in prometaphase until metaphase, chromosomes align and attach via their kinetochores to the mitotic spindle. Spindle assembly checkpoint regulation is crucial for further transition during mitosis. During anaphase, chromatids are pulled to opposite cell poles. In telophase, the new cells constrict, nuclear envelopes form, and chromosomes decondense. Immunofluorescence photographs were digitally enhanced. Size bars = 10 μm. (b) The four cell cycle phases are pivotally regulated by three major checkpoints, the G1/S and G2/M checkpoints and the spindle assembly checkpoint. A role for c-Rel is suggested during G2 or early M phase, as indicated. Before correct attachment of the mitotic spindle to the kinetochores (grey ellipse), the mitotic checkpoint complex proteins BubR1, Bub3, Cdc20, and Mad2 (blue) are located (among other proteins) at the kinetochore and inhibit activation of the anaphase-promoting complex or cyclosome (green). Thus, cyclin B/cyclin-dependent kinase 1 complexes (yellow/orange) remain active, and anaphase is inhibited (i.e., spindle assembly checkpoint activation). After correct attachment of the mitotic spindle (pink microtubules) to all kinetochores in metaphase, the anaphase-promoting complex or cyclosome gets activated, targeting cyclin B to degradation, inhibiting cyclin-dependent kinase 1 activity, and initiating the transition to anaphase. For the sake of clarity, not all proteins involved in spindle assembly checkpoint regulation are depicted here. APC/C, anaphase-promoting complex or cyclosome; CDK1, cyclin-dependent kinase 1; DAPI, 4′,6-diamidino-2-phenylindole. Journal of Investigative Dermatology 2016 136, 1090-1096DOI: (10.1016/j.jid.2016.02.003) Copyright © 2016 The Authors Terms and Conditions