IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing.

IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Research Abstract Details 

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IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Abstract Text:

Feng Zhu,Xiaojun Xia,Bigang Liu,Jianjun Shen,Yuhui Hu,Maria Person,Yinling Hu,

We recently reported that a large proportion of aggressive squamous cell carcinomas of humans and mice express markedly reduced IKKalpha. However, the role of IKKalpha in maintaining genomic stability is unknown. Here we reported that IKKalpha-deficient keratinocytes had a defect in the G(2)/M cell-cycle arrest in response to DNA damage due to downregulated 14-3-3sigma, a cell cycle checkpoint protein. Trimethylated histone H3 lysine 9 (H3-K9) was found to associate with the histone trimethyltransferase Suv39h1 and DNA methyltransferase Dnmt3a in the methylated 14-3-3sigma locus. Reintroduction of IKKalpha restored the expression of 14-3-3sigma. IKKalpha was found to associate with H3 in 14-3-3sigma, which prevented access of Suv39h1 to H3, thereby preventing hypermethylation of 14-3-3sigma. IKKalpha mutants that failed to bind to H3 did not restore the expression of 14-3-3sigma. Thus, IKKalpha protects the 14-3-3sigma locus from hypermethylation, which serves as a mechanism of maintaining genomic stability in keratinocytes.

IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Publishing Authors By Initials

F Zhu,X Xia,B Liu,J Shen,Y Hu,M Person,Y Hu,

For similar neoplasms: neoplasms by site: skin neoplasms research abstracts see: neoplasms: neoplasms by site: skin neoplasms research

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IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular cell

VOLUME: 27

Page Numbers: 214-27

Journal Abbreviation: Mol. Cell

ISSN: 1097-2765

DAY: 20

MONTH: Jul

YEAR: 2007

IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9802571

IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Keywords Mesh Terms:

KEYWORDS: Skin Neoplasms

MESH TERMS: metabolism

Chemical & Substance for Abstract: IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Information

Substance Name: I-kappa B Kinase

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing.

AFFILIATION: Science Park Research Division, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: ES07784

ACRONYM: ES

MEDLINETA: Mol Cell

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