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NO-sensitive guanylyl cyclase β1 subunit interacts with chromosomes during mitosis: novel role in the regulation of chromatin condensation
BMC Pharmacology volume 7, Article number: S43 (2007)
NO-sensitive guanylyl cyclase (GCNO), the major NO target, exists as an obligate heterodimer of one α and one β subunit. Two types of each subunit have been cloned (α1–2, β1–2), but only β1 and α subunit expression has been reported in the CNS. In this tissue, in situ hybridization studies have shown that β1 is more widespread than α subunits and in some areas is the only GCNO subunit expressed . Since β1/β1 homodimers are catalytically inactive the possibility of β1 having functions other than GCNO activity has been suggested. GCNO is predominantly cytosolic, however recent studies suggest that it can associate to membranes and other intracellular structures including nuclei [2, 3].
In the course of our studies on the cellular and sub-cellular distribution of GCNO subunits in CNS glial cells we have found that the β1 subunit is localized in the cytoplasm and the nucleus in cells that also express α subunits and present GCNO activity (astrocytes), as well as in cells devoid of α subunits and GCNO activity (microglia). In both cases GCNO β1 associates peripherally to chromosomes in all phases of mitosis and appears to regulate mitotic chromatin condensation independent of cGMP formation. Moreover, silencing by siRNA increases the percentage of cells in the S phase of the cell cycle and enhances proliferation.
The GCNO β1 subunit associates to chromosomes during mitosis and regulates chromatin condensation and cell cycle progression decreasing cell proliferation. This actions of GCNO β1 are independent of NO-dependent cGMP formation.
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This work has been supported by Ministerio de Educación y Ciencia, Spain, SAF2004-01717; Fellowship FPU 2000 to P. Pifarré.
Paula Pifarré, María Antonia Baltrons contributed equally to this work.
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Pifarré, P., Baltrons, M.A., Davalos, V. et al. NO-sensitive guanylyl cyclase β1 subunit interacts with chromosomes during mitosis: novel role in the regulation of chromatin condensation. BMC Pharmacol 7, S43 (2007). https://doi.org/10.1186/1471-2210-7-S1-S43
- Cell Cycle
- Glial Cell
- Cell Cycle Progression
- Chromatin Condensation
- Hybridization Study