Interaction between androgen receptor and coregulator SLIRP is regulated by Ack1 tyrosine kinase and androgen

Aberrant activation of the androgen receptor (AR) may play a critical role in castration resistant prostate cancer. After ligand binding, AR is recruited to the androgen responsive element (ARE) sequences on the DNA where AR interaction with coactivators and corepressors modulates transcription. We demonstrated that phosphorylation of AR at Tyr-267 by Ack1/TNK2 tyrosine kinase results in nuclear translocation, DNA binding, and androgen-dependent gene transcription in a low androgen environment. In order to dissect downstream mechanisms, we searched for proteins whose interaction with AR was regulated by Ack1. SLIRP (SRA stem-loop interacting RNA binding protein) was identified as a candidate protein. Interaction between AR and SLIRP was disrupted by Ack1 kinase activity as well as androgen or heregulin treatment. The noncoding RNA, SRA, was required for AR-SLIRP interaction. SLIRP was bound to ARE’s of AR target genes in the absence of androgen. Treatment with androgen or heregulin led to dissociation of SLIRP from the ARE. Whole transcriptome analysis of SLIRP knockdown in androgen responsive LNCaP cells showed that SLIRP affects a significant subset of androgen-regulated genes. Our data suggest that Ack1 kinase and androgen regulate interaction between AR and SLIRP and that SLIRP functions as a coregulator of AR with properties of a corepressor in a context-dependent manner

Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase

BACKGROUND: Telomeres consist of repetitive (TTAGGG) DNA sequences that are maintained by the multisubunit telomerase ribonucleoprotein. Telomerase consists of an RNA, which serves as template for the sequence tracts, and a catalytic subunit that functions in reverse transcription of the RNA template. Cloning and characterization of the human catalytic subunit of telomerase (hTERT) has supported a role in cell transformation. How telomerase activity is regulated, however, is largely unknown. RESULTS: We show here that hTERT associates directly with the c-Abl protein tyrosine kinase. We also found that c-Abl phosphorylates hTERT and inhibits hTERT activity. Moreover, our findings demonstrate that exposure of cells to ionizing radiation induces tyrosine phosphorylation of hTERT by a c-Abl-dependent mechanism. The functional significance of the c-Abl-hTERT interaction is supported by the demonstration that cells deficient in c-Abl show telomere lengthening. CONCLUSIONS: The ubiquitously expressed c-Abl tyrosine kinase is activated by DNA double-strand breaks. Our finding of telomere lengthening in c-Abl-deficient cells and the functional interactions between c-Abl and hTERT support a role for c-Abl in the regulation of telomerase function

Massive Charged Scalar Quasinormal Modes of Reissner-N\"ordstrom Black Hole Surrounded by Quintessence

We evaluate the complex frequencies of the normal modes for the massive charged scalar field perturbations around a Reissner-N\"ordstrom black hole surrounded by a static and spherically symmetric quintessence using third order WKB approximation approach. Due to the presence of quintessence, quasinormal frequencies damp more slowly. We studied the variation of quasinormal frequencies with charge of the black bole, mass and charge of perturbating scalar field and the quintessential state parameter.Comment: 9 pages, 9 figures and one tabl

Viscous-Inviscid Interactions in a Boundary-Layer Flow Induced by a Vortex Array

In this paper we investigate the asymptotic validity of boundary layer theory. For a flow induced by a periodic row of point-vortices, we compare Prandtl's solution to Navier-Stokes solutions at different $Re$ numbers. We show how Prandtl's solution develops a finite time separation singularity. On the other hand Navier-Stokes solution is characterized by the presence of two kinds of viscous-inviscid interactions between the boundary layer and the outer flow. These interactions can be detected by the analysis of the enstrophy and of the pressure gradient on the wall. Moreover we apply the complex singularity tracking method to Prandtl and Navier-Stokes solutions and analyze the previous interactions from a different perspective

Enhanced superconductivity in Hf-base metallic glasses

Systematic study of electrical resistivity of Hf_{100-x}Fe_x (x=20,25), Hf_{100-x}Cu_x (x=30,40,50), and Ti_{65}Cu_{35} metallic glasses has been done in the temperature range 0.3 K - 290 K, and in magnetic fields B <= 5 T. All Hf-base alloys are superconducting with T_c >= 0.44 K, which is well above T_c of pure crystalline Hf (0.13 K). From the initial slopes of the upper critical fields, (dH_{c2}/dT)_{T_c}, and resistivities we determined the dressed electronic densities of states, N_{\gamma}(E_F), for all alloys. Both T_c and N_{\gamma}(E_F) decrease with increasing x (Fe and Cu content). The results are compared with those for corresponding Zr-base metallic glasses and ion-implanted Hf films.Comment: 9 pages, 4 figures, 1 tabl