Abstract: A peptide is disclosed of the general structure: Z—W—Y, wherein Z and Y are independently a one to eight amino acid sequence wherein the amino acids are selected from glycine and alanine and W is a non-hydrolyzable pHis analogue. Such peptides can be used to produce sequence-independent anti-phosphohistidine antibodies. Also provided are antibodies that specifically bind to a peptide comprising a phosphohistidine (or a non-hydrolyzable pHis analogue) but fail to specifically bind to an identical peptide containing histidine instead of phosphohistidine.

Abstract: Isolated monoclonal antibodies and or antigen binding fragments thereof are disclosed herein that specifically bind polypeptides comprising a histidine phosphorylated at N3 (3-pHis). Nucleic acids encoding these antibodies, vectors including these nucleic acids, and host cells transformed with these vectors and nucleic acids are also disclosed. Methods are also disclosed for using these antibodies, such as for detection of polypeptides comprising a histidine phosphorylated at N3 (3-pHis). In some embodiments, the methods can be used to investigate signal transduction pathways.

Abstract: Isolated monoclonal antibodies and or antigen binding fragments thereof are disclosed herein that specifically bind polypeptides comprising a histidine phosphorylated at N3 (3-pHis). Nucleic acids encoding these antibodies, vectors including these nucleic acids, and host cells transformed with these vectors and nucleic acids are also disclosed. Methods are also disclosed for using these antibodies, such as for detection of polypeptides comprising a histidine phosphorylated at N3 (3-pHis). In some embodiments, the methods can be used to investigate signal transduction pathways.

Abstract: Isolated monoclonal antibodies and antigen binding fragments are disclosed herein that specifically bind polypeptides comprising a histidine phosphorylated at N3 (3-pHis). Nucleic acids encoding these antibodies, vectors including these nucleic acids, and host cells transformed with these vectors and nucleic acids are also disclosed. Methods are also disclosed for using these antibodies, such as for detection of polypeptides comprising a histidine phosphorylated at N3 (3-pHis), detection of a tumor, monitoring the effectiveness of therapeutic agent, and identifying antibiotics. In some embodiments, the methods can be used to investigate signal transduction pathways.

Abstract: A peptide is disclosed of the general structure: Z—W—Y, wherein Z and Y are independently a one to eight amino acid sequence wherein the amino acids are selected from glycine and alanine and W is a non-hydrolyzable pHis analogue. Such peptides can be used to produce sequence-independent anti-phosphohistidine antibodies. Also provided are antibodies that specifically bind to a peptide comprising a phosphohistidine (or a non-hydrolyzable pHis analogue) but fail to specifically bind to an identical peptide containing histidine instead of phosphohistidine.

Abstract: A peptide is disclosed of the general structure: Z—W—Y, wherein Z and Y are independently a one to eight amino acid sequence wherein the amino acids are selected from glycine and alanine and W is a non-hydrolyzable pHis analogue. Such peptides can be used to produce sequence-independent anti-phosphohistidine antibodies. Also provided are antibodies that specifically bind to a peptide comprising a phosphohistidine (or a non-hydrolyzable pHis analogue) but fail to specifically bind to an identical peptide containing histidine instead of phosphohistidine.

Abstract: Ubiquitin ligase wwp-1 and ubiquitin conjugating enzyme ubc-18 are identified in nematodes as mediators of dietary restriction induced longevity and therefore as targets for modulation of lifespan in animals. Methods of screening for compounds that modulate longevity by assaying wwp-1 ubiquitination pathway parameters are provided, as are related systems. In addition, methods of using wwp-1 and/or ubc-18 to modulate longevity or delay onset of age-related diseases are described.

Abstract: Ubiquitin ligase wwp-1 and ubiquitin conjugating enzyme ubc-18 are identified in nematodes as mediators of dietary restriction induced longevity and therefore as targets for modulation of lifespan in animals. Methods of screening for compounds that modulate longevity by assaying wwp-1 ubiquitination pathway parameters are provided, as are related systems. In addition, methods of using wwp-1 and/or ubc-18 to modulate longevity or delay onset of age-related diseases are described.

Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek gene to modulate both longevity and stress tolerance, are described.

Abstract: Provided herein are methods and compositions useful in the diagnosis and treatment of cancer. The methods and compositions typically involve detecting a level of phosphorylation of mTOR at serine 2481 in a subject and comparing the level of phosphorylation of mTOR at serine 2481 in said subject with a standard control.

Abstract: Ubiquitin ligase wwp-1 and ubiquitin conjugating enzyme ubc-18 are identified in nematodes as mediators of dietary restriction induced longevity and therefore as targets for modulation of lifespan in animals. Methods of screening for compounds that modulate longevity by assaying wwp-1 ubiquitination pathway parameters are provided, as are related systems. In addition, methods of using wwp-1 and/or ubc-18 to modulate longevity or delay onset of age-related diseases are described.

Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek gene to modulate both longevity and stress tolerance, are described.

Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek genet to modulate both longevity and stress tolerance, are described.

Abstract: A novel class of NIMA interacting proteins (PIN), exemplified by Pin1, is provided. Pin1 induces a G2 arrest and delays NIMA-induced mitosis when overexpressed, and triggers mitotic arrest and DNA fragmentation when depleted. Methods of identifying other Pin proteins and Pin-interacting proteins and identifying compositions which affect Pin activity or expression are also provided.

Abstract: A novel class of NIMA interacting proteins (PIN), exemplified by Pin1, is provided. Pin1 induces a G2 arrest and delays NIMA-induced mitosis when overexpressed, and triggers mitotic arrest and DNA fragmentation when depleted. Methods of identifying other Pin proteins and Pin-interacting proteins and identifying compositions which affect Pin activity or expression are also provided.

Abstract: A novel class of NIMA interacting proteins (PIN), exemplified by Pin1, is provided. Pin1 induces a G2 arrest and delays NIMA-induced mitosis when overexpressed, and triggers mitotic arrest and DNA fragmentation when depleted. Methods of identifying other Pin proteins and Pin-interacting proteins and identifying compositions which affect Pin activity or expression are also provided.

Abstract: A novel class of NIMA interacting proteins (PIN), exemplified by Pin1, is provided. Pin1 induces a G2 arrest and delays NIMA-induced mitosis when overexpressed, and triggers mitotic arrest and DNA fragmentation when depleted. Methods of identifying other Pin proteins and Pin-interacting proteins and identifying compositions which affect Pin activity or expression are also provided.

Abstract: A novel class of NIMA interacting proteins (PIN), exemplified by Pin1, is provided. Pin1 induces a G2 arrest and delays NIMA-induced mitosis when overexpressed, and triggers mitotic arrest and DNA fragmentation when depleted. Methods of identifying other Pin proteins and Pin-interacting proteins and identifying compositions which affect Pin activity or expression are also provided.

Abstract: A function for the human protein, Bsh3 was identified herein as being involved in mitosis. Thus, inhibitors of Bsh3 can be used for the treatment of cancer or other diseases marked by over-proliferation. Inhibitors of the yeast homolog (S. pombe Bsh3) can be used as anti-fungals. Alternatively, Bsh3 or Bsh3 activators may be used to activate proliferation in cells such as tissue culture cells and transplants.

Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek genet to modulate both longevity and stress tolerance, are described.