ABSTRACT
A hybrid comprising an autophagy-inducing peptide (AIP) and a cell-penetrating peptide (CPP) connected via heterodimeric leucine zippers was generated and delivered into cells. The hybrid successfully induced autophagy without significant cell death, while the same AIP directly connected to a CPP caused both autophagy and significant cell death.
Subject(s)
Autophagy/drug effects , Cell-Penetrating Peptides/chemistry , Leucine Zippers , Peptides/chemistry , Peptides/pharmacology , Amino Acid Sequence , HeLa Cells , Humans , Molecular Sequence Data , Peptides/administration & dosageABSTRACT
Rat models of human T-cell leukemia virus type 1 (HTLV-1)-related diseases such as adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis have been reported. However, these models do not completely reproduce human diseases partly because HTLV-1 replicates poorly in rats. We investigated here the possible reason for this. We found that the activity of Rex in rat cells is quite low compared to that in human cells. As Rex function depends largely on the CRM1 protein, whose human type (human CRM1 [hCRM1]) directly binds to Rex and exports it from the nucleus to the cytoplasm, we assessed whether rat CRM1 (rCRM1) could act as well as hCRM1 as a cofactor for Rex activity. We first cloned a cDNA encoding rCRM1 and found that both rCRM1 and hCRM1 could bind to and export Rex protein to the cytoplasm with similar efficiencies. However, unlike hCRM1, rCRM1 could hardly support Rex function because of its poor ability in inducing the Rex-Rex interaction required for RNA export into the cytoplasm. These observations suggest that the poor ability of rCRM1 to act as a cofactor for Rex function may be responsible for the poor replication of HTLV-1 in rats.
Subject(s)
Gene Products, rex/physiology , Human T-lymphotropic virus 1/physiology , Karyopherins/physiology , Receptors, Cytoplasmic and Nuclear , Amino Acid Sequence , Animals , Base Sequence , Cell Line , Cloning, Molecular , DNA Primers , Gene Products, rex/chemistry , Gene Products, rex/genetics , Humans , Molecular Sequence Data , Protein Binding , Protein Transport , Rats , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sequence Homology, Amino Acid , Virus Replication/physiology , Exportin 1 ProteinABSTRACT
Since the condition of a cancer patient in the terminal phase changes every day, it is difficult for patients at home to maintain stability unless symptom management and a support system are available. In order to reduce the anxiety of these patients and their families during this period and to support meaningful home care, a telephone consultation service of telephone calls from the Palliative Care Unit (PCU) was begun in October 1994. At this point, telephone calls have been made to 515 patients. The status of the telephone service last year (January to December 1999) is summarized herein. 1. Since patients and their families can contact the PCU at any time, they feel more secure. 2. Since patients and their families are telephoned from the PCU, they do not hesitate to consult the physician or nurse calling. 3. Physicians and nurses can ascertain a patient's condition and problems and cope with these aspects in a timely manner. 4. As a result, patients and their families can spend the time remaining in the patient's life with fewer symptoms suffered by the patient. In conclusion, this telephone consultation service has become an important system as part of the outpatient support system.
Subject(s)
Home Care Services , Neoplasms/therapy , Palliative Care/methods , Referral and Consultation , Telephone , Female , Humans , MaleABSTRACT
We investigated the role of human CRM1 (hCRM1) (exportin 1) in the function of Rex protein encoded by human T-cell leukemia virus type 1. hCRM1 promoted the export of Rex protein from the nucleus to the cytoplasm. A Rex protein with a mutation in the activation domain, RexM90, lost both the ability to bind to hCRM1 and the ability to multimerize. The overexpression of hCRM1 complemented the functional defects of RexM64, which contains a mutation in the multimerization domain of Rex. A dominant-negative mutant of Rex which sequesters cofactors of Rex abrogated multimerization as well as the activity of the wild-type Rex protein. These two functions were simultaneously restored by the overexpression of hCRM1. Taken together, these results suggest that hCRM1 plays important roles in the multimerization and export of Rex protein.
