PMID- 17015474 OWN - NLM STAT- MEDLINE DCOM- 20061113 LR - 20220225 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 26 IP - 20 DP - 2006 Oct TI - Differentiation-induced cleavage of Cutl1/CDP generates a novel dominant-negative isoform that regulates mammary gene expression. PG - 7466-78 AB - Cutl1/CCAAT displacement protein (CDP) is a transcriptional repressor of mouse mammary tumor virus (MMTV), a betaretrovirus that is a paradigm for mammary-specific gene regulation. Virgin mammary glands have high levels of full-length CDP (200 kDa) that binds to negative regulatory elements (NREs) to repress MMTV transcription. During late pregnancy, full-length CDP levels decline, and a 150-kDa form of CDP (CDP150) appears concomitantly with a decline in DNA-binding activity for the MMTV NREs and an increase in viral transcripts. Developmental regulation of CDP was recapitulated in the normal mammary epithelial line, SCp2. Western blotting of tissue and SCp2 nuclear extracts confirmed that CDP150 lacks the C terminus. Transfection of tagged full-length and mutant cDNAs into SCp2 cells and use of a cysteine protease inhibitor demonstrated that CDP is proteolytically processed within the homeodomain to remove the C terminus during differentiation. Mixing of virgin and lactating mammary extracts or transfection of mutant CDP cDNAs missing the homeodomain into cells containing full-length CDP also abrogated NRE binding. Loss of DNA binding correlated with increased expression of MMTV and other mammary-specific genes, indicating that CDP150 is a developmentally induced dominant-negative protein. Thus, a novel posttranslational process controls Cutl1/CDP activity and gene expression in the mammary gland. FAU - Maitra, Urmila AU - Maitra U AD - Section of Molecular Genetics and Microbiology, The University of Texas at Austin, 24th and Speedway, ESB 226, Austin, TX 78712-0162, USA. FAU - Seo, Jin AU - Seo J FAU - Lozano, Mary M AU - Lozano MM FAU - Dudley, Jaquelin P AU - Dudley JP LA - eng GR - R01CA34780/CA/NCI 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. DEP - 20060805 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Caseins) RN - 0 (Cux1 protein, mouse) RN - 0 (Homeodomain Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Protein Isoforms) RN - 0 (Repressor Proteins) RN - 9007-49-2 (DNA) RN - EC 3.4.22.- (Cysteine Endopeptidases) SB - IM MH - Animals MH - Caseins/metabolism MH - *Cell Differentiation MH - Cells, Cultured MH - Cysteine Endopeptidases/metabolism MH - DNA/metabolism MH - Female MH - Gene Deletion MH - *Gene Expression MH - Homeodomain Proteins/genetics/*metabolism MH - Mammary Glands, Animal/*cytology/*metabolism MH - Mammary Tumor Virus, Mouse/genetics MH - Mice MH - Nuclear Proteins/genetics/*metabolism MH - Pregnancy MH - Protein Binding MH - Protein Isoforms/genetics/metabolism MH - Repressor Proteins/genetics/*metabolism MH - Response Elements/genetics MH - Transcription, Genetic/genetics PMC - PMC1636867 EDAT- 2006/10/04 09:00 MHDA- 2006/11/14 09:00 PMCR- 2007/02/01 CRDT- 2006/10/04 09:00 PHST- 2006/10/04 09:00 [pubmed] PHST- 2006/11/14 09:00 [medline] PHST- 2006/10/04 09:00 [entrez] PHST- 2007/02/01 00:00 [pmc-release] AID - MCB.01083-06 [pii] AID - 1083-06 [pii] AID - 10.1128/MCB.01083-06 [doi] PST - ppublish SO - Mol Cell Biol. 2006 Oct;26(20):7466-78. doi: 10.1128/MCB.01083-06. Epub 2006 Aug 5.