scholarly journals The importance of ubiquitination and sumoylation on the transforming activity of HTLV Tax-1 and Tax-2

Retrovirology ◽  
2012 ◽  
Vol 9 (1) ◽  
Author(s):  
Linda Zane ◽  
Kuan-Teh Jeang
Keyword(s):  
Transforming Activity ◽  
Htlv Tax

scholarly journals The carboxyl-terminal CXXX sequence of Gi alpha, but not Rab5 or Rab11, supports Ras processing and transforming activity

1993 ◽  
Vol 268 (16) ◽  
pp. 11548-11552
Author(s):  
A.D. Cox ◽  
S.M. Graham ◽  
P.A. Solski ◽  
J.E. Buss ◽  
C.J. Der
Keyword(s):  
Transforming Activity ◽  
Carboxyl Terminal

scholarly journals The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Brianna J. Klein ◽  
Anagha Deshpande ◽  
Khan L. Cox ◽  
Fan Xuan ◽  
Mohamad Zandian ◽  
...  
Keyword(s):  
Critical Role ◽  
Cellular Transformation ◽  
Acute Leukemias ◽  
Hematopoietic Stem ◽  
Nucleosome Core ◽  
Stem And Progenitor Cells ◽  
Transforming Activity

AbstractChromosomal translocations of the AF10 (or MLLT10) gene are frequently found in acute leukemias. Here, we show that the PZP domain of AF10 (AF10PZP), which is consistently impaired or deleted in leukemogenic AF10 translocations, plays a critical role in blocking malignant transformation. Incorporation of functional AF10PZP into the leukemogenic CALM-AF10 fusion prevents the transforming activity of the fusion in bone marrow-derived hematopoietic stem and progenitor cells in vitro and in vivo and abrogates CALM-AF10-mediated leukemogenesis in vivo. Crystallographic, biochemical and mutagenesis studies reveal that AF10PZP binds to the nucleosome core particle through multivalent contacts with the histone H3 tail and DNA and associates with chromatin in cells, colocalizing with active methylation marks and discriminating against the repressive H3K27me3 mark. AF10PZP promotes nuclear localization of CALM-AF10 and is required for association with chromatin. Our data indicate that the disruption of AF10PZP function in the CALM-AF10 fusion directly leads to transformation, whereas the inclusion of AF10PZP downregulates Hoxa genes and reverses cellular transformation. Our findings highlight the molecular mechanism by which AF10 targets chromatin and suggest a model for the AF10PZP-dependent CALM-AF10-mediated leukemogenesis.

scholarly journals TRAF3 Is Required for NF-κB Pathway Activation Mediated by HTLV Tax Proteins

2019 ◽  
Vol 10 ◽  
Author(s):  
Stefania Fochi ◽  
Elisa Bergamo ◽  
Michela Serena ◽  
Simona Mutascio ◽  
Chloé Journo ◽  
...  
Keyword(s):  
Pathway Activation ◽  
Htlv Tax

scholarly journals A Mutation at Tyrosine 1062 in MEN2A-Ret and MEN2B-Ret Impairs Their Transforming Activity and Association with Shc Adaptor Proteins

1996 ◽  
Vol 271 (30) ◽  
pp. 17644-17649 ◽  
Author(s):  
Naoya Asai ◽  
Hideki Murakami ◽  
Toshihide Iwashita ◽  
Masahide Takahashi
Keyword(s):  
Adaptor Proteins ◽  
Transforming Activity

scholarly journals Transformation of mouse BALB 3T3 cells by enterobacterial plasmid misrepair gene mucAB.

1990 ◽  
Vol 10 (10) ◽  
pp. 5359-5364 ◽  
Author(s):  
M Tosu ◽  
H Tanooka
Keyword(s):  
Malignant Transformation ◽  
Cell Population ◽  
Nude Mice ◽  
Mouse Genome ◽  
Zinc Ions ◽  
3T3 Cells ◽  
Induced Expression ◽  
Whole Cell ◽  
Transformed Cell ◽  
Transforming Activity

The enterobacterial plasmid misrepair gene mucAB, ligated to the metal-inducible mammalian MT-1 promoter, was introduced into the genome of mouse BALB 3T3 cells. In the presence of zinc ions, MucA but not MucB protein was produced, and the whole-cell population of each mucAB+ clone started to show the transformation phenotype in a few days. Foci appeared in the transformed cell population after 4 weeks, and cells from the foci produced tumors in nude mice, indicating malignant transformation by the mucA product. Growth of mucAB+ cells was stimulated by zinc-induced expression of mucA. The transformation phenotype was reversed by removing zinc ions from the culture, indicating that the transformation was due not to MucA-mediated mutation in the mouse genome but to the direct transforming activity of MucA protein.

A small v-sis/platelet-derived growth factor (PDGF) B-protein domain in which subtle conformational changes abrogate PDGF receptor interaction and transforming activity

1990 ◽  
Vol 10 (10) ◽  
pp. 5496-5501
Author(s):  
N Giese ◽  
W J LaRochelle ◽  
M May-Siroff ◽  
K C Robbins ◽  
S A Aaronson
Keyword(s):  
Monoclonal Antibody ◽  
Growth Factor ◽  
Conformational Changes ◽  
Protein Domain ◽  
Platelet Derived Growth Factor ◽  
Receptor Interaction ◽  
Pdgf Receptor ◽  
Amino Acid Residues ◽  
Disulfide Linkages ◽  
Transforming Activity

Deletion scanning mutagenesis within the transforming region of the v-sis oncogene was used to dissect structure-function relationships. Mutations affecting codons within a domain encoding amino acids 136 through 148 had no effect upon homodimer formation or recognition by antisera which detect determinants dependent upon native intrachain disulfide linkages, yet the same mutations completely abolished transforming activity. A platelet-derived growth factor B (PDGF B) monoclonal antibody that prevents its interaction with PDGF receptors recognized v-sis, delta 142 (deletion of codon 142), and delta 148 but not delta 136, delta 137, or delta 139 mutants. These findings mapped the epitope recognized by this monoclonal antibody to include amino acid residues 136 to 139. Furthermore, mutations in the codon 136 to 148 domain caused markedly impaired ability to induce PDGF receptor tyrosine phosphorylation. Thus, subtle conformational alterations in this small domain critically affect PDGF receptor recognition and/or functional activation.

Specific activation of the cellular Harvey-ras oncogene in dimethylbenzanthracene-induced mouse mammary tumors

1986 ◽  
Vol 6 (11) ◽  
pp. 4104-4108
Author(s):  
S Dandekar ◽  
S Sukumar ◽  
H Zarbl ◽  
L J Young ◽  
R D Cardiff
Keyword(s):  
Mammary Tumors ◽  
3T3 Cells ◽  
Mouse Mammary Tumor ◽  
Mouse Mammary Tumors ◽  
Transforming Activity ◽  
Radiation Induced ◽  
Genomic Dnas ◽  
Nih 3T3 ◽  
Adenosine Nucleotide ◽  
Nih 3T3 Cells

Genomic DNAs from dimethylbenzanthracene-induced BALB/c mouse mammary tumors arising from the transplantable hyperplastic outgrowth (HPO) line designated DI/UCD transformed NIH 3T3 cells upon transfection. Transforming activity was attributed to the presence of activated Harvey ras-1 oncogenes containing an A----T transversion at the middle adenosine nucleotide in codon 61. DNAs from untreated DI/UCD HPO cells and radiation-induced and spontaneous mammary tumors from the DI/UCD HPO line failed to transform NIH 3T3 cells. The results indicated that the mutation activation of Harvey ras-1 oncogenes was specific to dimethylbenzanthracene treatment in the mouse mammary tumor system.

Mutational analysis of a ras catalytic domain

1986 ◽  
Vol 6 (7) ◽  
pp. 2646-2654
Author(s):  
B M Willumsen ◽  
A G Papageorge ◽  
H F Kung ◽  
E Bekesi ◽  
T Robins ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Mutational Analysis ◽  
Nucleotide Binding ◽  
Membrane Localization ◽  
Wide Range ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Transforming Activity ◽  
Type V

We used linker insertion-deletion mutagenesis to study the catalytic domain of the Harvey murine sarcoma virus v-rasH transforming protein, which is closely related to the cellular rasH protein. The mutants displayed a wide range of in vitro biological activity, from those that induced focal transformation of NIH 3T3 cells with approximately the same efficiency as the wild-type v-rasH gene to those that failed to induce any detectable morphologic changes. Correlation of transforming activity with the location of the mutations enabled us to identify three nonoverlapping segments within the catalytic domain that were dispensable for transformation and six other segments that were required for transformation. Segments that were necessary for guanosine nucleotide (GDP) binding corresponded to three of the segments that were essential for transformation; two of the three segments share strong sequence homology with other purine nucleotide-binding proteins. Loss of GDP binding was associated with apparent instability of the protein. Lesions in two of the three other required regions significantly reduced GDP binding, while small lesions in the last required region did not impair GDP binding or membrane localization. We speculate that this latter region interacts with the putative cellular target of ras. The results suggest that transforming ras proteins require membrane localization, guanosine nucleotide binding, and an additional undefined function that may represent interaction with their target.

The myristylation signal of p60v-src functionally complements the N-terminal fps-specific region of P130gag-fps

1989 ◽  
Vol 9 (5) ◽  
pp. 2214-2219
Author(s):  
A R Brooks-Wilson ◽  
E Ball ◽  
T Pawson
Keyword(s):  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Specific Region ◽  
Protein Tyrosine Kinases ◽  
Membrane Association ◽  
Modular Construction ◽  
Specific Domain ◽  
Protein Tyrosine ◽  
Sarcoma Virus ◽  
Transforming Activity

The P130gag-fps protein-tyrosine kinase of Fujinami sarcoma virus contains an N-terminal fps-specific domain (Nfps) that is important for oncogenicity. The N-terminal 14 amino acids of p60v-src, which direct myristylation and membrane association, can replace the gag-Nfps sequences of P130gag-fps (residues 1 to 635), producing a highly transforming src-fps polypeptide. Conversely, gag-Nfps can restore modest transforming activity to a nonmyristylated v-src polypeptide. These results emphasize the modular construction of protein-tyrosine kinases and indicate that Nfps, possibly in conjunction with gag, functions in the subcellular localization of P130gag-fps.

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