PUBLICATION
Evolutionary relationships and functional conservation among vertebrate Max-associated proteins: the zebrafish homolog of Mxi1
- Authors
- Schreiber-Agus, N., Chin, L., Chen, K., Torres, R., Thomson, C.T., Sacchettini, J.C., and DePinho, R.A.
- ID
- ZDB-PUB-961014-1004
- Date
- 1994
- Source
- Oncogene 9(11): 3167-3177 (Journal)
- Registered Authors
- DePinho, Ronald A.
- Keywords
- none
- MeSH Terms
-
- Base Sequence
- Tumor Suppressor Proteins
- Basic-Leucine Zipper Transcription Factors
- Repressor Proteins*
- Molecular Sequence Data
- Humans
- Genes, Tumor Suppressor
- Animals
- Embryonic Development
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
- Helix-Loop-Helix Motifs
- Zebrafish
- Basic Helix-Loop-Helix Transcription Factors
- Zebrafish Proteins
- DNA-Binding Proteins/genetics*
- DNA-Binding Proteins/physiology
- Structure-Activity Relationship
- Biological Evolution*
- Transcription Factors*
- DNA, Complementary
- Amino Acid Sequence
- PubMed
- 7936639
Citation
Schreiber-Agus, N., Chin, L., Chen, K., Torres, R., Thomson, C.T., Sacchettini, J.C., and DePinho, R.A. (1994) Evolutionary relationships and functional conservation among vertebrate Max-associated proteins: the zebrafish homolog of Mxi1. Oncogene. 9(11):3167-3177.
Abstract
In mammals, current evidence supports the view that Myc- responsive activities are regulated in part through an intracellular balance between levels of transcriptionally- active Myc/Max heterodimers and those of transcriptionally- inert Max/Max, Mad/Max and Mxi1/Max complexes. To gain insight into the roles of Mad and Mxi1 in cellular growth and differentiation and to fortify key structure-function relationships from an evolutionary standpoint, low stringency hybridization screens were used to identify potential homologs of these Max-associated proteins in the zebra fish genome. A single class of cDNA clones that cross-hybridized both to human mad and mxi1 probes was shown to encode a putative protein with significantly greater homology to mammalian Mxi1 than to Mad, particularly in the basic and helix-loop-helix (bHLH) regions. The high degree of structural relatedness between vertebrate Mxi1 proteins apparent in molecular modelling studies was consistent with the findings that the HLH/leucine zipper (LZ) region of zMxi1 exhibited the same profile of dimerization specificities as its mammalian counterpart in the two-hybrid system and that zmxi1 could, like human mxi1 (Lahoz et al., 1994), suppress the oncogenic potential of mouse c-myc in a mammalian cell. Finally, a comparison of steady-state zc-myc and zmxi1 mRNA levels during zebra fish embryogenesis demonstrated (i) high levels of zc-myc relative to zmxi1 mRNA during initiation of organogenesis, a period characterized by intense growth and active differentiation and (ii) rising levels of zmxi1 mRNA during progression towards the terminally differentiated state. These contrasting patterns of developmental expression together with the capacity of zmxi1 to repress myc-induced transformation support a model for the regulation, by Max-associated proteins, of Myc functions in the control of normal cell development and neoplastic growth.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping