Domains of human c-myc protein required for autosuppression and cooperation with ras oncogenes are overlapping

1990 ◽  
Vol 10 (9) ◽  
pp. 4961-4966
Author(s):  
L J Penn ◽  
M W Brooks ◽  
E M Laufer ◽  
T D Littlewood ◽  
J P Morgenstern ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dna Binding ◽  
Gene Transcription ◽  
Leucine Zipper ◽  
Rat Embryo ◽  
Helix Loop Helix ◽  
Myc Gene ◽  
Ras Oncogenes ◽  
Carboxyl Terminal ◽  
Basic Region

Amino acids 106 to 143 and 354 to 433 of the human c-myc protein (439 amino acids) were shown to be required for the protein to suppress c-myc gene transcription and were found to exactly overlap with those necessary for c-myc to cooperate with ras oncogenes in the transformation of rat embryo fibroblasts. The essential carboxyl-terminal region harbors structural motifs (a basic region, a helix-loop-helix motif, and a "leucine zipper"), which, in other proteins, can mediate dimerization and sequence-specific DNA binding.

scholarly journals Domains of human c-myc protein required for autosuppression and cooperation with ras oncogenes are overlapping.

1990 ◽  
Vol 10 (9) ◽  
pp. 4961-4966 ◽  
Author(s):  
L J Penn ◽  
M W Brooks ◽  
E M Laufer ◽  
T D Littlewood ◽  
J P Morgenstern ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dna Binding ◽  
Gene Transcription ◽  
Leucine Zipper ◽  
Rat Embryo ◽  
Helix Loop Helix ◽  
Myc Gene ◽  
Ras Oncogenes ◽  
Carboxyl Terminal ◽  
Basic Region

Amino acids 106 to 143 and 354 to 433 of the human c-myc protein (439 amino acids) were shown to be required for the protein to suppress c-myc gene transcription and were found to exactly overlap with those necessary for c-myc to cooperate with ras oncogenes in the transformation of rat embryo fibroblasts. The essential carboxyl-terminal region harbors structural motifs (a basic region, a helix-loop-helix motif, and a "leucine zipper"), which, in other proteins, can mediate dimerization and sequence-specific DNA binding.

scholarly journals Identification of C/EBP basic region residues involved in DNA sequence recognition and half-site spacing preference.

1993 ◽  
Vol 13 (11) ◽  
pp. 6919-6930 ◽  
Author(s):  
P F Johnson
Keyword(s):  
Amino Acids ◽  
Dna Binding ◽  
Dna Sequence ◽  
Leucine Zipper ◽  
Alpha Helix ◽  
Binding Characteristics ◽  
Hybrid Proteins ◽  
Sequence Recognition ◽  
Basic Region ◽  
Half Site

C/EBP and GCN4 are basic region-leucine zipper (bZIP) DNA-binding proteins that recognize the dyad-symmetric sequences ATTGCGCAAT and ATGAGTCAT, respectively. The sequence specificities of these and other bZIP proteins are determined by their alpha-helical basic regions, which are related at the primary sequence level. To identify amino acids that are responsible for the different DNA sequence specificities of C/EBP and GCN4, two kinds of hybrid proteins were constructed: GCN4-C/EBP chimeras fused at various positions in the basic region and substitution mutants in which GCN4 basic region amino acids were replaced by the corresponding residues from C/EBP. On the basis of the DNA-binding characteristics of these hybrid proteins, three residues that contribute significantly to the differences in C/EBP and GCN4 binding specificity were defined. These residues are clustered along one face of the basic region alpha helix. Two of these specificity residues were not identified as DNA-contacting amino acids in a recently reported crystal structure of a GCN4-DNA complex, suggesting that the residues used by C/EBP and GCN4 to make base contacts are not identical. A random binding site selection procedure also was used to define the optimal recognition sequences for three of the GCN4-C/EBP fusion proteins. These experiments identify an element spanning the hinge region between the basic region and leucine zipper domains that dictates optimal half-site spacing (either directly abutted for C/EBP or overlapping by one base pair for GCN4) in high-affinity binding sites for these two proteins.

Identification of C/EBP basic region residues involved in DNA sequence recognition and half-site spacing preference

1993 ◽  
Vol 13 (11) ◽  
pp. 6919-6930
Author(s):  
P F Johnson
Keyword(s):  
Amino Acids ◽  
Dna Binding ◽  
Dna Sequence ◽  
Leucine Zipper ◽  
Alpha Helix ◽  
Binding Characteristics ◽  
Hybrid Proteins ◽  
Sequence Recognition ◽  
Basic Region ◽  
Half Site

C/EBP and GCN4 are basic region-leucine zipper (bZIP) DNA-binding proteins that recognize the dyad-symmetric sequences ATTGCGCAAT and ATGAGTCAT, respectively. The sequence specificities of these and other bZIP proteins are determined by their alpha-helical basic regions, which are related at the primary sequence level. To identify amino acids that are responsible for the different DNA sequence specificities of C/EBP and GCN4, two kinds of hybrid proteins were constructed: GCN4-C/EBP chimeras fused at various positions in the basic region and substitution mutants in which GCN4 basic region amino acids were replaced by the corresponding residues from C/EBP. On the basis of the DNA-binding characteristics of these hybrid proteins, three residues that contribute significantly to the differences in C/EBP and GCN4 binding specificity were defined. These residues are clustered along one face of the basic region alpha helix. Two of these specificity residues were not identified as DNA-contacting amino acids in a recently reported crystal structure of a GCN4-DNA complex, suggesting that the residues used by C/EBP and GCN4 to make base contacts are not identical. A random binding site selection procedure also was used to define the optimal recognition sequences for three of the GCN4-C/EBP fusion proteins. These experiments identify an element spanning the hinge region between the basic region and leucine zipper domains that dictates optimal half-site spacing (either directly abutted for C/EBP or overlapping by one base pair for GCN4) in high-affinity binding sites for these two proteins.

The DNA target determines the dimerization partner selected by bHLHZ-like hybrid proteins AhRJun and ArntFos

2017 ◽  
Vol 13 (3) ◽  
pp. 476-488 ◽  
Author(s):  
Ichiro Inamoto ◽  
Gang Chen ◽  
Jumi A. Shin
Keyword(s):  
Gene Regulation ◽  
Transcription Factors ◽  
Dna Binding ◽  
Molecular Basis ◽  
Leucine Zipper ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Hybrid Proteins ◽  
Protein Partner ◽  
Basic Region

The molecular basis of protein–partner selection and DNA binding of the basic helix–loop–helix (bHLH) and basic region-leucine zipper (bZIP) superfamilies of dimeric transcription factors is fundamental toward understanding gene regulation.

scholarly journals The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells

1991 ◽  
Vol 11 (12) ◽  
pp. 6286-6295
Author(s):  
R Alani ◽  
P Brown ◽  
B Binétruy ◽  
H Dosaka ◽  
R K Rosenberg ◽  
...  
Keyword(s):  
Amino Acids ◽  
Leucine Zipper ◽  
Transcriptional Regulator ◽  
Dna Binding Domain ◽  
Rat Embryo ◽  
Ras Gene ◽  
N Terminus ◽  
Embryo Cells ◽  
Normal Rat ◽  
Nuclear Phosphoprotein

The nuclear phosphoprotein c-Jun, encoded by the proto-oncogene c-jun, is a major component of the AP-1 complex. A potent transcriptional regulator, c-jun is also able to transform normal rat embryo cells in cooperation with an activated c-Ha-ras gene. By deletion analysis, we identified the regions of c-Jun encoding transformation and transactivation functions. Our studies indicate that there is a direct correlation between the ability of the c-Jun protein to activate transcription and cotransform rat embryo cells. The regions involved in these functions include the conserved leucine zipper/DNA binding domain and an effector domain near its N terminus. This N-terminal region spans amino acids 61 to 146 of the c-Jun protein and is highly conserved among all Jun family members. These results support the hypothesis that c-Jun transforms cells by stimulating the expression of transformation-mediating genes.

scholarly journals The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells.

1991 ◽  
Vol 11 (12) ◽  
pp. 6286-6295 ◽  
Author(s):  
R Alani ◽  
P Brown ◽  
B Binétruy ◽  
H Dosaka ◽  
R K Rosenberg ◽  
...  
Keyword(s):  
Amino Acids ◽  
Leucine Zipper ◽  
Transcriptional Regulator ◽  
Dna Binding Domain ◽  
Rat Embryo ◽  
Ras Gene ◽  
N Terminus ◽  
Embryo Cells ◽  
Normal Rat ◽  
Nuclear Phosphoprotein

The nuclear phosphoprotein c-Jun, encoded by the proto-oncogene c-jun, is a major component of the AP-1 complex. A potent transcriptional regulator, c-jun is also able to transform normal rat embryo cells in cooperation with an activated c-Ha-ras gene. By deletion analysis, we identified the regions of c-Jun encoding transformation and transactivation functions. Our studies indicate that there is a direct correlation between the ability of the c-Jun protein to activate transcription and cotransform rat embryo cells. The regions involved in these functions include the conserved leucine zipper/DNA binding domain and an effector domain near its N terminus. This N-terminal region spans amino acids 61 to 146 of the c-Jun protein and is highly conserved among all Jun family members. These results support the hypothesis that c-Jun transforms cells by stimulating the expression of transformation-mediating genes.

scholarly journals Enhancement by lithium of cAMP-induced CRE/CREB-directed gene transcription conferred by TORC on the CREB basic leucine zipper domain

2007 ◽  
Vol 408 (1) ◽  
pp. 69-77 ◽  
Author(s):  
Ulrike Böer ◽  
Julia Eglins ◽  
Doris Krause ◽  
Susanne Schnell ◽  
Christof Schöfl ◽  
...  
Keyword(s):  
Dna Binding ◽  
Gene Transcription ◽  
Leucine Zipper ◽  
Luciferase Reporter ◽  
Lithium Salts ◽  
Transactivation Domain ◽  
Camp Response Element ◽  
Basic Leucine Zipper ◽  
Response Element ◽  
Leucine Zipper Domain

The molecular mechanism of the action of lithium salts in the treatment of bipolar disorder is not well understood. As their therapeutic action requires chronic treatment, adaptive neuronal processes are suggested to be involved. The molecular basis of this are changes in gene expression regulated by transcription factors such as CREB (cAMP-response-element-binding protein). CREB contains a transactivation domain, in which Ser119 is phosphorylated upon activation, and a bZip (basic leucine zipper domain). The bZip is involved in CREB dimerization and DNA-binding, but also contributes to CREB transactivation by recruiting the coactivator TORC (transducer of regulated CREB). In the present study, the effect of lithium on CRE (cAMP response element)/CREB-directed gene transcription was investigated. Electrically excitable cells were transfected with CRE/CREB-driven luciferase reporter genes. LiCl (6 mM or higher) induced an up to 4.7-fold increase in 8-bromo-cAMP-stimulated CRE/CREB-directed transcription. This increase was not due to enhanced Ser119 phosphorylation or DNA-binding of CREB. Also, the known targets inositol monophosphatase and GSK3β (glycogen-synthase-kinase 3β) were not involved as specific GSK3β inhibitors and inositol replenishment did not mimic and abolish respectively the effect of lithium. However, lithium no longer enhanced CREB activity when the CREB-bZip was deleted or the TORC-binding site inside the CREB-bZip was specifically mutated (CREB-R300A). Otherwise, TORC overexpression conferred lithium responsiveness on CREB-bZip or the CRE-containing truncated rat somatostatin promoter. This indicates that lithium enhances cAMP-induced CRE/CREB-directed transcription, conferred by TORC on the CREB-bZip. We thus support the hypothesis that lithium salts modulate CRE/CREB-dependent gene transcription and suggest the CREB coactivator TORC as a new molecular target of lithium.

scholarly journals mTFE3, an X-linked transcriptional activator containing basic helix-loop-helix and zipper domains, utilizes the zipper to stabilize both DNA binding and multimerization.

1992 ◽  
Vol 12 (2) ◽  
pp. 817-827 ◽  
Author(s):  
C Roman ◽  
A G Matera ◽  
C Cooper ◽  
S Artandi ◽  
S Blain ◽  
...  
Keyword(s):  
Dna Binding ◽  
Heavy Chain ◽  
Leucine Zipper ◽  
Immunoglobulin Heavy Chain ◽  
Functional Roles ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
The Individual ◽  
Bhlh Proteins ◽  
High Degree

Southwestern (DNA-protein) screening of a murine L-cell cDNA library by using a probe for the microE3 site in the immunoglobulin heavy-chain enhancer yielded a clone, mTFE3, which is a member of the subset of basic helix-loop-helix (BHLH) proteins that also contain a leucine zipper (ZIP). Since the individual contribution of these domains is not well understood for proteins which contain them both, mutational analyses were performed to assess the functional roles of the HLH and ZIP regions for DNA binding and multimerization. The HLH region is stringently required for DNA binding but not for multimerization. The ZIP region is not stringently required for binding or multimerization, but stabilizes both multimer formation and DNA binding. A high degree of conservation at both the amino acid and nucleotide levels between the human transcription factor TFE3 and mTFE3 suggests that mTFE3 is the murine homolog of human TFE3. By using fluorescent in situ hybridization, mTFE3 was mapped to mouse chromosome X in band A2, which is just below the centromere. We show that in addition to the immunoglobulin heavy-chain microE3 site, mTFE3 binds to transcriptional elements important for lymphoid-specific, muscle-specific, and ubiquitously expressed genes. Binding of mTFE3 to DNA induces DNA bending.

scholarly journals TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family.

1991 ◽  
Vol 5 (12a) ◽  
pp. 2342-2352 ◽  
Author(s):  
D E Fisher ◽  
C S Carr ◽  
L A Parent ◽  
P A Sharp
Keyword(s):  
Dna Binding ◽  
Leucine Zipper ◽  
Helix Loop Helix
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