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The genetically haploid spermatids are functionally diploid as a result of the sharing of gene products through their intercellular bridges. This movement of molecules among haploid cells is crucial for the production of spermatozoa since numerous essential proteins are encoded on sex chromosomes. Testis-brain RNA-binding protein (TB-RBP) is a single-stranded DNA- and RNA-binding protein prominent in the nuclei and cytoplasm of specific stages of differentiating male germ cells. Here we present evidence that TB-RBP moves from the nucleus to the cytoplasm and through intercellular bridges of male germ cells. based on its RNA-binding capabilities, we propose a role for TB-RBP in the distribution of equal amounts of mRNAs in haploid male germ cells. Key Words: spermatogenesis; RNA-binding proteins; haploid gene expression; mRNA movement.

Heat shock protein 90 (HSP90) is involved in the regulation of diverse biological processes such as cell signaling, proliferation and survival, and has been recently recognized as a potential target for cancer therapy. Ganetespib is a potent ATP competitive inhibitor of HSP90. Ganetespib downregulated the expression of multiple signal transducing molecules including EGFR, IGF-1R, c-Met, Akt, B-RAF and C-RAF, resulting in pronounced decrease in phosphorylation of Akt and Erk1/2 in a panel of five cutaneous melanoma cell lines including those harboring B-RAF and N-RAS mutations. Ganetespib exhibited potent antiproliferative activity on all five of these cell lines, with IC50 values between 37.5 and 84 nM. Importantly, Ganetespib is active on B-RAF mutated melanoma cells that have acquired resistance to B-RAF inhibition. Ganetespib induced apoptosis and cell cycle arrest at G1 and/or G2/M phase. Ganetespib induced cell cycle arrest was accompanied by altered expression of cyclin-dependent kinase inhibitor (CDKI) p21Cip1 and p27Kip1, cyclins B1, D1 and E, and/or cyclin-dependent kinases 1, 2 and 4. HSP90 is functionally important for melanoma cells and HSP90 inhibitors such as ganetespib could potentially be effective therapeutics for melanoma with various genetic mutations and acquired resistance to B-RAF inhibition.