A double point mutation in the DNA-binding region of Egr2 switches its function from inhibition to induction of proliferation: A potential contribution to the development of congenital hypomyelinating neuropathy

2006 ◽  
Vol 24 (1) ◽  
pp. 159-169 ◽  
Author(s):  
Peter Arthur-Farraj ◽  
Rhona Mirsky ◽  
David B. Parkinson ◽  
Kristjan R. Jessen
Keyword(s):  
Dna Binding ◽  
Point Mutation ◽  
Double Point ◽  
Potential Contribution ◽  
Binding Region ◽  
Congenital Hypomyelinating Neuropathy

A second c-myb protein is translated from an alternatively spliced mRNA expressed from normal and 5'-disrupted myb loci

1989 ◽  
Vol 9 (12) ◽  
pp. 5456-5463 ◽  
Author(s):  
G L Shen-Ong ◽  
B Lüscher ◽  
R N Eisenman
Keyword(s):  
Dna Binding ◽  
Nuclear Dna ◽  
Dna Binding Protein ◽  
Major Protein ◽  
Tumor Cell Lines ◽  
Binding Region ◽  
Large Intron ◽  
Alternatively Spliced ◽  
Myb Genes ◽  
Cryptic Splice Sites

The major protein encoded by the c-myb oncogene in many species has been identified as an unstable, nuclear DNA-binding protein with an apparent molecular mass of 75 to 80 kilodaltons (p75c-myb). Recently, an alternatively spliced form of c-myb-encoded mRNA has been identified in murine cells containing either normal or rearranged c-myb genes. This mRNA includes a new exon, termed E6A, formed through use of cryptic splice sites located in the large intron between c-myb exons vE6 and vE7. E6A is predicted to contribute an internal 121-residue in-frame insertion into a region C terminal of the DNA-binding domain the c-myb-encoded protein. Here we report the identification of an 85-kilodalton (p85c-myb-E6A) protein as the translation product of the alternatively spliced E6A c-myb mRNA. This protein as well as p75c-myb were precipitated with anti-Myb antibodies raised against the conserved DNA-binding region of c-Myb. Proteolytic mapping studies showed that the two proteins are highly related but not identical. However, only the p85 protein reacted with an antiserum prepared against the E6A region expressed in bacteria, demonstrating that p85 but not p75 contains E6A sequences. In addition, the mobilities of both p85 and p75 were increased in myeloid tumor cell lines containing proviral integrations upstream of the 5' coding exons of v-myb, indicating that both proteins are truncated forms of c-Myb expressed from the same disrupted allele. p75c-myb and p85c-myb-E6A were indistinguishable with respect to nuclear localization and protein half-life. Furthermore, both forms of Myb were synthesized continuously throughout the cell cycle in 70Z ore-B cells. The contribution of the E6A domain to c-myb function remains to be elucidated.

Analysis of the essential and excision repair functions of the RAD3 gene of Saccharomyces cerevisiae by mutagenesis

1986 ◽  
Vol 6 (4) ◽  
pp. 1218-1227
Author(s):  
L Naumovski ◽  
E C Friedberg
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Binding ◽  
Excision Repair ◽  
Random Mutagenesis ◽  
Nucleotide Binding ◽  
Yeast Cells ◽  
Wild Type ◽  
Binding Region ◽  
Site Specific ◽  
Essential Function

The RAD3 gene of Saccharomyces cerevisiae, which is involved in excision repair of DNA and is essential for cell viability, was mutagenized by site-specific and random mutagenesis. Site-specific mutagenesis was targeted to two regions near the 5' and 3' ends of the coding region, selected on the basis of amino acid sequence homology with known nucleotide binding and with known specific DNA-binding proteins, respectively. Two mutations in the putative nucleotide-binding region and one in the putative DNA-binding region inactivate the excision repair function of the gene, but not the essential function. A gene encoding two tandem mutations in the putative DNA-binding region is defective in both excision repair and essential functions of RAD3. Seven plasmids were isolated following random mutagenesis with hydroxylamine. Mutations in six of these plasmids were identified by gap repair of mutant plasmids from the chromosome of strains with previously mapped rad3 mutations, followed by DNA sequencing. Three of these contain missense mutations which inactivate only the excision repair function. The other three carry nonsense mutations which inactivate both the excision repair and essential functions. Collectively our results indicate that the RAD3 excision repair function is more sensitive to inactivation than is the essential function. Overexpression of wild-type Rad3 protein and a number of rad3 mutant proteins did not affect the UV resistance of wild-type yeast cells. However, overexpression of Rad3-2 protein rendered wild-type cells partially UV sensitive, indicating that excess Rad3-2 protein is dominant to the wild-type form. These and other results suggest that Rad3-2 protein retains its affinity for damaged DNA or other substrates, but is not catalytically active in excision repair.

scholarly journals Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding.

1992 ◽  
Vol 12 (12) ◽  
pp. 5581-5592 ◽  
Author(s):  
E Shaulian ◽  
A Zauberman ◽  
D Ginsberg ◽  
M Oren
Keyword(s):  
Dna Binding ◽  
Point Mutation ◽  
P53 Gene ◽  
Dominant Negative ◽  
Mutant P53 ◽  
Wild Type ◽  
Transforming Activity ◽  
Wild Type P53 ◽  
Negative Dominance

Mutations in the p53 gene are most frequent in cancer. Many p53 mutants possess transforming activity in vitro. In cells transformed by such mutants, the mutant protein is oligomerized with endogenous cell p53. To determine the relevance of oligomerization for transformation, miniproteins containing C-terminal portions of p53 were generated. These miniproteins, although carrying no point mutation, transformed at least as efficiently as full-length mutant p53. Transforming activity was coupled with the ability to oligomerize with wild-type p53, as well as with the ability to abrogate sequence-specific DNA binding by coexpressed wild-type p53. These findings suggest that p53-mediated transformation may operate through a dominant negative mechanism, involving the generation of DNA binding-incompetent oligomers.

scholarly journals Point mutation in the mouse glucocorticoid receptor preventing DNA binding impairs spatial memory

2001 ◽  
Vol 98 (22) ◽  
pp. 12790-12795 ◽  
Author(s):  
M. S. Oitzl ◽  
H. M. Reichardt ◽  
M. Joels ◽  
E. R. de Kloet
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Spatial Memory ◽  
Point Mutation

Establishment of an apoptosis-sensitive rat mammary carcinoma cell line with a mutation in the DNA-binding region of p53

2006 ◽  
Vol 232 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Tetsuya Hamaguchi ◽  
Yoichiro Matsuoka ◽  
John Bechberger ◽  
Takamasa Ohnishi ◽  
Ken-ichi Fujita ◽  
...  
Keyword(s):  
Dna Binding ◽  
Cell Line ◽  
Mammary Carcinoma ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line ◽  
Mammary Carcinoma Cell ◽  
Binding Region ◽  
Mammary Carcinoma Cell Line

scholarly journals A double point mutation in PCL-γ1 (Y509A/F510A) enhances Y783 phosphorylation and inositol phospholipid-hydrolyzing activity upon EGF stimulation

2010 ◽  
Vol 42 (3) ◽  
pp. 216 ◽  
Author(s):  
Sang-Hee Chung ◽  
Sung-Kuk Kim ◽  
Jung Kuk Kim ◽  
Yong-Ryoul Yang ◽  
Pann-Ghill Suh ◽  
...  
Keyword(s):  
Point Mutation ◽  
Double Point ◽  
Inositol Phospholipid
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