PMID- 16951149
OWN - NLM
STAT- MEDLINE
DCOM- 20071126
LR  - 20201209
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 17
DP  - 2006 Sep 1
TI  - Multiple endocrine neoplasia type 1 interacts with forkhead transcription factor 
      CHES1 in DNA damage response.
PG  - 8397-403
AB  - 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.
FAU - Busygina, Valeria
AU  - Busygina V
AD  - Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, 
      USA.
FAU - Kottemann, Molly C
AU  - Kottemann MC
FAU - Scott, Kenneth L
AU  - Scott KL
FAU - Plon, Sharon E
AU  - Plon SE
FAU - Bale, Allen E
AU  - Bale AE
LA  - eng
GR  - R01-GM57426/GM/NIGMS NIH HHS/United States
GR  - R01-GM66079/GM/NIGMS NIH HHS/United States
GR  - T32-GM008753/GM/NIGMS NIH HHS/United States
GR  - T32-GM08307/GM/NIGMS NIH HHS/United States
GR  - T32-HD07149-29/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Drosophila Proteins)
RN  - 0 (FOXN3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Mnn1 protein, Drosophila)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Repressor Proteins)
SB  - IM
EIN - Cancer Res. 2006 Dec 15;66(24):12039
MH  - Animals
MH  - Cell Cycle Proteins/*genetics/metabolism
MH  - Cell Division
MH  - Cell Line
MH  - *DNA Damage
MH  - DNA, Neoplasm/*genetics
MH  - Drosophila Proteins/genetics
MH  - Drosophila melanogaster/genetics
MH  - Forkhead Transcription Factors
MH  - G2 Phase
MH  - Humans
MH  - Larva
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/pathology
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Repressor Proteins/*genetics/metabolism
MH  - Transfection
EDAT- 2006/09/05 09:00
MHDA- 2007/12/06 09:00
CRDT- 2006/09/05 09:00
PHST- 2006/09/05 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2006/09/05 09:00 [entrez]
AID - 66/17/8397 [pii]
AID - 10.1158/0008-5472.CAN-06-0061 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Sep 1;66(17):8397-403. doi: 10.1158/0008-5472.CAN-06-0061.