CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible switch for DNA binding

The proline-rich homeodomain protein (PRH/Hex) regulates transcription by binding to specific DNA sequences and regulates mRNA transport by binding to translation initiation factor eIF4E. Protein kinase CK2 plays multiple roles in the regulation of gene expression and cell proliferation. Here, we show that PRH interacts with the β subunit of CK2 in vitro and in cells and that CK2 phosphorylates PRH. Phosphorylation of PRH by CK2 inhibits the DNA binding activity of this protein and dephosphorylation restores DNA binding indicating that this modification acts as a reversible switch. We show that phosphorylation of the homeodomain is sufficient to block DNA binding and we identify two amino acids within this the domain that are phosphorylated by CK2: S163 and S177. Site-directed mutagenesis demonstrates that mutation of either of these residues to glutamic acid partially mimics phosphorylation but is insufficient to completely block DNA binding whereas an S163E/S177E double mutation severely inhibits DNA binding. Significantly, the S163E and S177E mutations and the S163E/S177E double mutation all inhibit the ability of PRH to regulate transcription in cells. Since these amino acids are conserved between many homeodomain proteins, our results suggest that CK2 may regulate the activity of several homeodomain proteins in this manner

PRH/Hex: an oligomeric transcription factor and ,ultifunctional regulator of cell fate.

The PRH (proline-rich homeodomain) [also known as Hex (haematopoietically expressed homeobox)] protein is a critical regulator of vertebrate development. PRH is able to regulate cell proliferation and differentiation and is required for the formation of the vertebrate body axis, the haematopoietic and vascular systems and the formation of many vital organs. PRH is a DNAbinding protein that can repress and activate the transcription of its target genes using multiple mechanisms. In addition, PRH can regulate the nuclear transport of specific mRNAs making PRH a member of a select group of proteins that control gene expression at the transcriptional and translational levels. Recent biophysical analysis of the PRH protein has shown that it forms homo-oligomeric complexes in vivo and in vitro and that the proline-rich region of PRH forms a novel dimerization interface. Here we will review the current literature on PRH and discuss the complex web of interactions centred on this multifunctional protein

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Detection of subclinical atherosclerosis and diastolic dysfunction in patients with schizophrenia

Cüneyt Ünsal,1 Mustafa Oran,2 Hande Oktay Tureli,3 Seref Alpsoy,4 Sema Yesilyurt,5 Mehtap Arslan,6 Birol Topcu,7 Osman Karakaya,8 Erhan Kurt6 1Department of Psychiatry, Namik Kemal University, School of Medicine, Tekirdag, Turkey; 2Department of Internal Medicine, Namik Kemal University, School of Medicine, Tekirdag, Turkey; 3Department of Cardiology, Bakirkoy Dr Sadi Konuk Education and Research Hospital, Istanbul, Turkey; 4Department of Cardiology, Namik Kemal University, School of Medicine, Tekirdag, Turkey; 5Department of Psychiatry, Bağcilar Training and Research Hospital, Istanbul, Turkey; 6Department of Psychiatry, Bakirkoy Training and Research Hospital for Psychiatry Neurology and Neurosurgery, Istanbul, Turkey; 7Department of Biostatistics, Namik Kemal University, School of Medicine, Tekirdag, Turkey; 8Department of Social Service, Yalova University, Faculty of Economics and Administrative Sciences, Yalova, Turkey Background: Patients with schizophrenia have a higher risk for cardiovascular diseases, which is associated with early mortality compared with the nonschizophrenic population. Early diagnosis of cardiovascular diseases in asymptomatic periods in patients with schizophrenia would enhance their quality of life and reduce mortality. Echocardiography, carotid ultrasonography, and ankle brachial index (ABI) measurement are known to be beneficial methods of detecting subclinical cardiovascular diseases and of risk stratification. The present study investigated carotid intima media thickness (CIMT) and ABI and echocardiographic parameters measured via conventional and tissue Doppler echocardiography in patients with schizophrenia in comparison with a control group. Methods: The present case-control study included 116 patients with schizophrenia and 88 healthy patients. Participants with any current comorbid psychiatric disorder, current or lifetime neurological and medical problems, current coronary artery disease, diabetes, hypertension, hypothyroidism, or hyperthyroidism or who were using antihypertensives, antidiabetic agents, or antiobesity drugs were excluded. High-resolution B-mode ultrasound images were used to measure CIMT. Conventional and tissue Doppler measurements were performed according to the recommendations of the American Society of Echocardiography. Results: Low ABI, mitral ratio of the early (E) to late (A) ventricular filling velocities, septal E´, septal S´, lateral E´, lateral S´, septal E´/septal A´, lateral E´/lateral A´, and high septal A´, mitral E/septal E´, mitral E/lateral E´, and CIMT values were observed in the schizophrenia group compared with the control group. Conclusion: Doppler parameters supported the hypothesis that patients with schizophrenia are at high risk for cardiovascular diseases. Keywords: schizophrenia, carotid intima media thickness, ankle brachial index, tissue Doppler echocardiograph