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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.

SUBMITTER: Chin L

PROVIDER: S-EPMC41182 | biostudies-other | 1995 Aug

REPOSITORIES: biostudies-other

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

Chin L L Schreiber-Agus N N Pellicer I I Chen K K Lee H W HW Dudast M M Cordon-Cardo C C DePinho R A RA

Proceedings of the National Academy of Sciences of the United States of America 19950801 18

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 ...[more]

PMID: 7667316

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Project description:The decision to provide parental care is often associated with trade-offs, because resources allocated to parental care typically cannot be invested in self-maintenance or mating. In most animals, females provide more parental care than males, but the reason for this pattern is still debated in evolutionary ecology. To better understand sex differences in parental care and its consequences, we need to study closely related species where the sexes differ in offspring care. We investigated parental care in relation to offspring growth in two closely related coucal species that fundamentally differ in sex roles and parental care, but live in the same food-rich habitat with a benign climate and have a similar breeding phenology. Incubation patterns differed and uniparental male black coucals fed their offspring two times more often than female and male white-browed coucals combined. Also, white-browed coucals had more 'off-times' than male black coucals, during which they perched and preened. However, these differences in parental care were not reflected in offspring growth, probably because white-browed coucals fed their nestlings a larger proportion of frogs than insects. A food-rich habitat with a benign climate may be a necessary, but-perhaps unsurprisingly-is not a sufficient factor for the evolution of uniparental care. In combination with previous results (Goymann et al. 2015 J. Evol. Biol. 28, 1335-1353 (doi:10.1111/jeb.12657)), these data suggest that white-browed coucals may cooperate in parental care, because they lack opportunities to become polygamous rather than because both parents were needed to successfully raise all offspring. Our case study supports recent theory suggesting that permissive environmental conditions in combination with a particular life history may induce sexual selection in females. A positive feedback loop among sexual selection, body size and adult sex-ratio may then stabilize reversed sex roles in competition and parental care.

Dataset Information

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

Publications

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

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