This Article Full Text Full Text (PDF) Correction (v66,p12039) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Busygina, V. Articles by Bale, A. E. Search for Related Content PubMed PubMed Citation Articles by Busygina, V. Articles by Bale, A. E.

Multiple Endocrine Neoplasia Type 1 Interacts with Forkhead Transcription Factor CHES1 in DNA Damage Response

Departments of ¹ Genetics and ² Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut and ³ Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas

Requests for reprints: Allen E. Bale, Department of Genetics, Yale University School of Medicine, 333 Cedar Street, SHM I-321, New Haven, CT 06510. Phone: 203-785-5746; Fax: 203-785-7227; E-mail: allen.bale{at}yale.edu.

Multiple endocrine neoplasia type 1 (MEN1) is a cancer susceptibility syndrome affecting several endocrine tissues. Investigations of the biochemical function of the MEN1 protein, menin, have suggested a role as a transcriptional comodulator. The mechanism by which MEN1 inactivation leads to tumor formation is not fully understood. MEN1 was implicated to function in both regulation of cell proliferation and maintenance of genomic integrity. Here, we investigate the mechanism by which MEN1 affects DNA damage response. We found that Drosophila larval tissue and mouse embryonic fibroblasts mutant for the MEN1 homologue were deficient for a DNA damage-activated S-phase checkpoint. The forkhead transcription factor CHES1 (FOXN3) was identified as an interacting protein by a genetic screen, and overexpression of CHES1 restored both cell cycle arrest and viability of MEN1 mutant flies after ionizing radiation exposure. We showed a biochemical interaction between human menin and CHES1 and showed that the COOH terminus of menin, which is frequently mutated in MEN1 patients, is necessary for this interaction. Our data indicate that menin is involved in the activation of S-phase arrest in response to ionizing radiation. CHES1 is a component of a transcriptional repressor complex, that includes mSin3a, histone deacetylase (HDAC) 1, and HDAC2, and it interacts with menin in an S-phase checkpoint pathway related to DNA damage response. (Cancer Res 2006; 66(17): 8397-402)

This article has been cited by other articles:

				MEN1 Interacts with CHES1 in DNA Damage Response Cancer Res., December 15, 2006; 66(24): 12039 - 12039. [Full Text] [PDF]