CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC. These data confirm that CRPC commonly remains dependent on ligand-activated AR signaling.

Abstract. The neuronal microtubule-associated protein tau is required for the development of cell polarity in cultured neurons. Using PC12 cells that stably express tau and tau amino-terminal fragments, we report that tau interacts with the neural plasma membrane through its amino-terminal projection domain. In differentiated PC12 transfectants, tau is found in growth cone-like structures in a nonmicrotubule-dependent manner. In hippocampal neurons, tau is differentially extracted by detergent and enriched in the growth cone and the distal axon when membrane is left intact. In PC12 transfectants, overexpression of tau's amino-terminal fragment, but not of full-length tau, suppresses NGF-induced process formation. Our data suggest that tau's amino-terminal projection domain has an important role in neuritic development and establishes tau as a mediator of microtubule-plasma membrane interactions.

Tau protein is a family of microtubule binding proteins, heterogeneous in molecular weight, that are induced during neurite outgrowth and are found prominently in neurofibrillary tangles in Alzheimer's disease. The predicted amino acid sequences of two forms of tau protein from mouse brain were determined from complementary DNA clones. These forms are identical in their amino-terminal sequences but differ in their carboxyl-terminal domains. Both proteins contain repeated sequences that may be tubulin binding sites. The sequence suggests that tau is an elongated molecule with no extensive alpha-helical or beta-sheet domains. These complementary DNAs should enable the study of various functional domains of tau and the study of tau expression in normal and pathological states.

We have determined the nucleotide sequence of two Bacillus subtilis promoters (veg and tms) that are utilized by the principal form of B. subtilis RNA polymerase found in vegetative cells (sigma 55-RNA polymerase) and have compared our sequences to those of several previously reported Bacillus promoters. Hexanucleotide sequences centered approximately 35 (the "--35" region) and 10 (the "--10" region) base pairs upstream from the veg and tms transcription starting points (and separated by 17 base pairs) corresponded closely to the consensus hexanucleotides (TTGACA and TATAAT) attributed to Escherichia coli promoters. Conformity to the preferred --35 and --10 sequences may not be sufficient to promote efficient utilization by B. subtilis RNA polymerase, however, since three promoters (veg, tms and E. coli tac) that conform to these sequences and that are utilized efficiently by E. coli RNA polymerase were used with highly varied efficiencies by B. subtilis RNA polymerase. We have also analyzed mRNA sequences in DNA located downstream from eight B. subtilis chromosomal and phage promoters for nucleotide sequences that might signal the initiation of translation. In accordance with the rules of McLaughlin, Murray and Rabinowitz (1981), we observe mRNA nucleotide sequences with extensive complementarity to the 3' terminal region of B. subtilis 16S rRNA, followed by an initiation codon and an open reading frame.