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Multiple endocrine neoplasia type 1 interacts with forkhead transcription factor CHES1 in DNA damage response.
Cancer Res. 2006 Sep 01; 66(17):8397-403.CR

Abstract

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.

Authors+Show Affiliations

Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16951149

Citation

Busygina, Valeria, et al. "Multiple Endocrine Neoplasia Type 1 Interacts With Forkhead Transcription Factor CHES1 in DNA Damage Response." Cancer Research, vol. 66, no. 17, 2006, pp. 8397-403.
Busygina V, Kottemann MC, Scott KL, et al. Multiple endocrine neoplasia type 1 interacts with forkhead transcription factor CHES1 in DNA damage response. Cancer Res. 2006;66(17):8397-403.
Busygina, V., Kottemann, M. C., Scott, K. L., Plon, S. E., & Bale, A. E. (2006). Multiple endocrine neoplasia type 1 interacts with forkhead transcription factor CHES1 in DNA damage response. Cancer Research, 66(17), 8397-403.
Busygina V, et al. Multiple Endocrine Neoplasia Type 1 Interacts With Forkhead Transcription Factor CHES1 in DNA Damage Response. Cancer Res. 2006 Sep 1;66(17):8397-403. PubMed PMID: 16951149.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple endocrine neoplasia type 1 interacts with forkhead transcription factor CHES1 in DNA damage response. AU - Busygina,Valeria, AU - Kottemann,Molly C, AU - Scott,Kenneth L, AU - Plon,Sharon E, AU - Bale,Allen E, PY - 2006/9/5/pubmed PY - 2007/12/6/medline PY - 2006/9/5/entrez SP - 8397 EP - 403 JF - Cancer research JO - Cancer Res VL - 66 IS - 17 N2 - 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. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/16951149/Multiple_endocrine_neoplasia_type_1_interacts_with_forkhead_transcription_factor_CHES1_in_DNA_damage_response_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16951149 DB - PRIME DP - Unbound Medicine ER -