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PMID:22001116

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Citation

Marzinke, MA and Clagett-Dame, M (2012) The all-trans retinoic acid (atRA)-regulated gene Calmin (Clmn) regulates cell cycle exit and neurite outgrowth in murine neuroblastoma (Neuro2a) cells. Exp. Cell Res. 318:85-93

Abstract

The vitamin A metabolite all-trans retinoic acid (atRA) functions in nervous system development and regulates cell proliferation and differentiation. Neuroblastoma cells (SH-SY5Y and Neuro2a or N2A) exposed to atRA undergo growth inhibition and neuronal differentiation, both of which are preceded by an increase in Clmn mRNA. Treatment of N2A cells with atRA produces a reduction in phosphohistone 3 immunostaining and BrdU incorporation, both indicators of a reduction in cell proliferation. These effects are nearly eliminated in atRA-treated shClmn knockdown cells. Loss of Clmn in the mouse N2A cell line also results in a significant reduction of atRA-mediated neurite outgrowth, a response that can be rescued by reintroduction of the Clmn sequence. In contrast, ectopic overexpression of Clmn produces an increase in the cyclin dependent kinase inhibitor, p21(Cip1), a decrease in cyclin D1 protein and an increase in hypophosphorylated Rb, showing that Clmn participates in G(1)/S arrest. Clmn overexpression alone is sufficient to inhibit N2A cell proliferation, whereas both Clmn and atRA must be present to induce neurite outgrowth. This study shows that the atRA-responsive gene Clmn promotes exit from the cell cycle, a requisite event for neuronal differentiation.

Links

PubMed Online version:10.1016/j.yexcr.2011.10.002

Keywords

Animals; Cell Cycle/drug effects; Cell Cycle/physiology; Cell Cycle Proteins/metabolism; Cell Differentiation/drug effects; Cell Proliferation/drug effects; Gene Expression Regulation, Neoplastic/drug effects; Gene Knockdown Techniques; Humans; Membrane Proteins/deficiency; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Neurites/drug effects; Neurites/pathology; Neuroblastoma/pathology; RNA, Messenger/biosynthesis; RNA, Messenger/genetics; RNA, Messenger/metabolism; Tretinoin/pharmacology; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CLMN

acts_upstream_of_or_within

GO:0008285: negative regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CLMN

acts_upstream_of_or_within

GO:0031175: neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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