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New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding.

ABSTRACT: Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44-67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (KD 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention.

SUBMITTER: Foca A

PROVIDER: S-EPMC4613256 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding.

Focà Annalia A Sanguigno Luca L Focà Giuseppina G Strizzi Luigi L Iannitti Roberta R Palumbo Rosanna R Hendrix Mary J C MJ Leonardi Antonio A Ruvo Menotti M Sandomenico Annamaria A

International journal of molecular sciences 20150907 9

Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to bloc ...[more]

PMID: 26370966

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Project description:Simple Summary R-ice is one of the world’s most important staples; a growing population and declining rates of growth in rice yields will present significant challenges ahead. After the heading stage, the photosynthetic ability of the flag leaf has a great effect on the yield of rice, and this ability can be evaluated by leaf color, chlorophyll content, quantum yield, etc. Our purpose was to screen candidate genes that affect photosynthetic efficiency through QTL mapping analysis and predict their function through protein interaction and homology sequence analysis. The results suggest that OsbHLHq11 may be involved in chlorophyll accumulation and enhancing photosynthetic efficiency, which may lead to high yields. Abstract Photosynthesis is an important factor in determining the yield of rice. In particular, the size and efficiency of the photosynthetic system after the heading has a great impact on the yield. Research related to high-efficiency photosynthesis is essential to meet the growing demands of crops for the growing population. Chlorophyll is a key molecule in photosynthesis, a pigment that acts as an antenna to absorb light energy. Improvement of chlorophyll content characteristics has been emphasized in rice breeding for several decades. It is expected that an increase in chlorophyll content may increase photosynthetic efficiency, and understanding the genetic basis involved is important. In this study, we measured leaf color (CIELAB), chlorophyll content (SPAD), and chlorophyll fluorescence, and quantitative trait loci (QTL) mapping was performed using 120 Cheongcheong/Nagdong double haploid (CNDH) line after the heading date. A major QTL related to chlorophyll content was detected in the RM26981-RM287 region of chromosome 11. OsbHLHq11 was finally selected through screening of genes related to chlorophyll content in the RM26981-RM287 region. The relative expression level of the gene of OsbHLHq11 was highly expressed in cultivars with low chlorophyll content, and is expected to have a similar function to BHLH62 of the Gramineae genus. OsbHLHq11 is expected to increase photosynthetic efficiency by being involved in the chlorophyll content, and is expected to be utilized as a new genetic resource for breeding high-yield rice.

Dataset Information

New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding.

Publications

New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding.

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