Contrasting roles for Myc and Mad proteins in cellular growth and differentiation Journal Article
| Authors: | Chin, L.; Schreiber-Agus, N.; Pellicer, I.; Chen, K.; Lee, H. W.; Dudast, M.; Cordon-Cardo, C.; DePinho, R. A. |
| Article Title: | Contrasting roles for Myc and Mad proteins in cellular growth and differentiation |
| Abstract: | The positive effects of Myc on cellular growth and gene expression are antagonized by activities of another member of the Myc superfamily, Mad. Characterization of the mouse homolog of human mad on the structural level revealed that domains shown previously to be required in the human protein for anti-Myc repression, sequence-specific DNA-binding activity, and dimerization with its partner Max are highly conserved. Conservation is also evident on the biological level in that both human and mouse mad can antagonize the ability of c-myc to cooperate with ras in the malignant transformation of cultured cells. An analysis of c-myc and mad gene expression in the developing mouse showed contrasting patterns with respect to tissue distribution and developmental stage. Regional differences in expression were more striking on the cellular level, particularly in the mouse and human gastrointestinal system, wherein c-Myc protein was readily detected in immature proliferating cells at the base of the colonic crypts, while Mad protein distribution was restricted to the postmitotic differentiated cells in the apex of the crypts. An increasing gradient of Mad was also evident in the more differentiated subcorneal layers of the stratified squamous epithelium of the skin. Together, these observations support the view that both downregulation of Myc and accumulation of Mad may be necessary for progression of precursor cells to a growth-arrested, terminally differentiated state. |
| Keywords: | controlled study; human cell; dna-binding proteins; nonhuman; protein localization; cell proliferation; animal cell; mouse; animal; mice; cell division; cell growth; cell maturation; embryo; cell differentiation; animalia; cell transformation, neoplastic; skin; molecular sequence data; species specificity; cell transformation; myc protein; gene repression; rat; newborn; fibroblast; intestine epithelium cell; rats; proto-oncogene proteins c-myc; intestines; oncogene myc; crypt cell; squamous epithelium; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 92 |
| Issue: | 18 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1995-08-29 |
| Start Page: | 8488 |
| End Page: | 8492 |
| Language: | English |
| DOI: | 10.1073/pnas.92.18.8488 |
| PUBMED: | 7667316 |
| PROVIDER: | scopus |
| PMCID: | PMC41182 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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