PMID- 12169273 OWN - NLM STAT- MEDLINE DCOM- 20020913 LR - 20190707 IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 278 IP - 2 DP - 2002 Aug 15 TI - Menin's interaction with glial fibrillary acidic protein and vimentin suggests a role for the intermediate filament network in regulating menin activity. PG - 175-83 AB - Recently the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor gene was cloned. Its protein product, called menin, has been shown to associate with the AP1 transcription factor JunD and to repress JunD-mediated transcription. However, little is known concerning the regulation of menin. Here we report that menin interacts with the type III intermediate filament (IF) proteins glial fibrillary acidic protein (GFAP) and vimentin. Menin's interaction with these IF proteins was characterized and confirmed both in vitro and in vivo using GST pull-down analysis, co-immunoprecipitation experiments, and immunofluorescence studies. Deletion mutants of GFAP or vimentin involving the head domains of the molecules abolish the interaction with menin. Endogenous menin is colocalized with GFAP and vimentin in glioma cells as determined by confocal microscopy. Furthermore, a tailless GFAP deletion mutant, which disrupts the IF network, results in menin/GFAP/vimentin-containing aggregates. Triple immunofluorescence labeling studies with antibodies against menin, BrdU, and GFAP show that menin and GFAP colocalize in glioma cells at the S-G2 phase of the cell cycle, as measured by BrdU incorporation. Our data suggest that the intermediate filament network interacts with and may serve as a cytoplasmic sequestering network for menin at the S and early G2 phase of the cell cycle. FAU - Lopez-Egido, Juan AU - Lopez-Egido J AD - Department of Medical Sciences, Endocrine Oncology Unit, Uppsala University Hospital, S-751 85 Uppsala, Sweden. FAU - Cunningham, Janet AU - Cunningham J FAU - Berg, Mikael AU - Berg M FAU - Oberg, Kjell AU - Oberg K FAU - Bongcam-Rudloff, Erik AU - Bongcam-Rudloff E FAU - Gobl, Anders AU - Gobl A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (MEN1 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Vimentin) SB - IM MH - Gene Library MH - Glial Fibrillary Acidic Protein/genetics/*metabolism MH - Humans MH - Intermediate Filaments/*physiology MH - Interphase MH - Microscopy, Fluorescence MH - Mutation MH - Neoplasm Proteins/*metabolism MH - Protein Binding MH - *Proto-Oncogene Proteins MH - Tumor Cells, Cultured MH - Two-Hybrid System Techniques MH - Vimentin/genetics/*metabolism EDAT- 2002/08/10 10:00 MHDA- 2002/09/14 10:01 CRDT- 2002/08/10 10:00 PHST- 2002/08/10 10:00 [pubmed] PHST- 2002/09/14 10:01 [medline] PHST- 2002/08/10 10:00 [entrez] AID - S0014482702955758 [pii] AID - 10.1006/excr.2002.5575 [doi] PST - ppublish SO - Exp Cell Res. 2002 Aug 15;278(2):175-83. doi: 10.1006/excr.2002.5575.