Contrasting roles for Myc and Mad proteins in cellular growth and differentiation

Lynda Chin, Nicole Schreiber-Agus, Inmaculada Pellicer, Ken Chen, Han Woong Lee, Maria Dudast, Carlos Cordon-Cardo, Ronald A. Depinho

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)8488-8492
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number18
DOIs
Publication statusPublished - 1995 Aug 29

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Growth
Proteins
Proto-Oncogene Proteins c-myc
Gene Expression
myc Genes
Dimerization
Tissue Distribution
Cultured Cells
Down-Regulation
Epithelium
Skin

All Science Journal Classification (ASJC) codes

  • Genetics
  • General

Cite this

Chin, Lynda ; Schreiber-Agus, Nicole ; Pellicer, Inmaculada ; Chen, Ken ; Lee, Han Woong ; Dudast, Maria ; Cordon-Cardo, Carlos ; Depinho, Ronald A. / Contrasting roles for Myc and Mad proteins in cellular growth and differentiation. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 18. pp. 8488-8492.
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Contrasting roles for Myc and Mad proteins in cellular growth and differentiation. / Chin, Lynda; Schreiber-Agus, Nicole; Pellicer, Inmaculada; Chen, Ken; Lee, Han Woong; Dudast, Maria; Cordon-Cardo, Carlos; Depinho, Ronald A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 18, 29.08.1995, p. 8488-8492.

Research output: Contribution to journalArticle

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