Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch.

Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch. Abstract Text:

Mudit Kakar,Amy B Cadwallader,James R Davis,Carol S Lim,

PURPOSE: The purpose of this study was to understand the mechanism of nuclear export of the protein switch, used for controlled intracellular delivery of gene products, by studying the involvement of classical export receptor CRM1. METHOD: Transient transfections of protein switch constructs, isolated nuclear export and import signals were carried out. Effect of leptomycin B (inhibitor of export receptor) and geldanamycin (inhibitor of Hsp90) on localization of these constructs was studied using fluorescence microscopy. Putative nuclear export signals in the glucocorticoid and progesterone receptor ligand binding domains were identified and studied. RESULTS: It was observed that treatment with leptomycin B caused nuclear accumulation of the protein switch constructs. However, geldanamycin did not have any pronounced effect on the localization. The isolated nuclear export signal from glucocorticoid receptor localized mostly in the cytoplasm, while its mutated version was present everywhere. CONCLUSION: The localization controlled protein switch constructs are exported out of the nucleus by the classical CRM1 receptors. The ligand binding domain of these protein switch constructs plays an important role in maintaining these constructs in the cytoplasm in the absence of ligand, as well the re-export back to the cytoplasm from the nucleus after ligand washout.

Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch. Publishing Authors By Initials

M Kakar,AB Cadwallader,JR Davis,CS Lim,

For similar proteins: receptors, cytoplasmic and nuclear research abstracts see: proteins: receptors, cytoplasmic and nuclear research

PUBMED ID PMID:

MEDLINE DATE:

Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Pharmaceutical research

VOLUME: 24

Page Numbers: 2146-55

Journal Abbreviation: Pharm. Res.

ISSN: 0724-8741

DAY: 13

MONTH: 06

YEAR: 2007

Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8406521

Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch. Keywords Mesh Terms:

KEYWORDS: Receptors, Cytoplasmic and Nuclear

MESH TERMS: physiology

Chemical & Substance for Abstract: Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch. Information

Substance Name: exportin 1 protein

Registry Number: 0

Grant and Affiliation Information for Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch.

AFFILIATION: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way #318, Salt Lake City, UT 84108, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK070060

ACRONYM: DK

MEDLINETA: Pharm Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch Related Publications

• A 68-kDa kinase and NADPH oxidase component p67phox are targets for Cdc42Hs and Rac1 in neutrophils.
• A Comparison Between Directional and Proportional Methods in Locating Acupuncture Points Using Dual-Energy X-ray Absorptiometry in Korean Women.
• A brain serine/threonine protein kinase activated by Cdc42 and Rac1.
• A case of needle tract implantation of hepatocellular carcinoma after percutaneous biopsy with an 18G Tru-cut needle.
• A diagnosis system for the spinal column nerve damaged patients.
• Alpha-tocopheryl succinate, in contrast to alpha-tocopherol and alpha-tocopheryl acetate, inhibits prostaglandin E2 production in human lung epithelial cells.
• Approach to hypokalemia.
• Beta1PIX, the PAK-interacting exchange factor, requires localization via a coiled-coil region to promote microvillus-like structures and membrane ruffles.
• Combined fibrinolysis using reduced-dose alteplase plus abciximab with immediate rescue angioplasty versus primary angioplasty with adjunct use of abciximab for the treatment of acute myocardial infarction: Asia-Pacific Acute Myocardial Infarction Trial (
• Controlling protein compartmentalization to overcome disease.
• Cryptic Rac-binding and p21(Cdc42Hs/Rac)-activated kinase phosphorylation sites of NADPH oxidase component p67(phox).
• Diffusion tensor imaging in children with fetal alcohol spectrum disorders.
• Disruption of hippocampal connectivity in children and adolescents with schizophrenia--a voxel-based diffusion tensor imaging study.
• GMF-knockout mice are unable to induce brain-derived neurotrophic factor after exercise.
• Identification and molecular cloning of a p21cdc42/rac1-activated serine/threonine kinase that is rapidly activated by thrombin in platelets.
• Interaction between PAK and nck: a template for Nck targets and role of PAK autophosphorylation.
• Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family.
• NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain.
• Novel p21-activated kinase-dependent protrusions characteristically formed at the edge of transformed cells.
• PAK kinases are directly coupled to the PIX family of nucleotide exchange factors.
• PAK promotes morphological changes by acting upstream of Rac.
• Preliminary study for gait phases detection to develop a rehabilitation equipment for hemiplegic patients.
• Reduced severity of experimental autoimmune encephalomyelitis in GMF-deficient mice.
• Removal of senescent cells from organisms: A way to retard aging or just nonsense?
• Risk of mistaken DNR orders.
• Role of reactive oxygen species in the induction of apoptosis by alpha-tocopheryl succinate.
• The molecular basis of ageing in stem cells.
• The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family.
• [Recent progress in abdominal CT imaging]
• [Test on the cost and development on the payment system of home health care nursing]