Intracellular localization and nucleocytoplasmic trafficking of steroid receptors: an overview.
Subcellular compartmentalization and dynamic movements of steroid receptors are major steps in executing their transcription regulatory function. Though significant progress has been made in understanding the mechanisms underlying nuclear import of NLS-bearing proteins, our general and mechanistic understanding about the nuclear export processes has begun to emerge only recently. The discovery of most commonly utilized CRM1/exportin1 dependent nuclear export pathway is attributed to a potent nuclear export inhibitor leptomycin B that helped dissecting this and other nuclear export pathways. Simultaneously, utilization of green fluorescent protein (GFP)-tagged intracellular steroid receptors has contributed to not only resolving controversial issue of subcellular localization of unliganded hormone receptors but also provided further insight into finer details of receptor dynamics in living cells. With judicious use of leptomycin B and expression of GFP-tagged receptors in living cells, existence of exportin1/CRM1 independent pathway(s), nuclear export signals and receptors for bi-directional translocation that are unique to steroid receptor trafficking have been specified. Currently, we appear to be arriving at a consensus that steroid/nuclear receptors follow dynamic nucleocytoplasmic processes that deviate from the ones commonly utilized by majority of other proteins.
Kumar
Sanjay
S
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India.
Saradhi
Mallampati
M
Chaturvedi
Nagendra K
NK
Tyagi
Rakesh K
RK
D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D028884:Karyopherins / Q000502:physiology; D008954:Models, Biological; D021381:Protein Transport / Q000502:physiology; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D011987:Receptors, Steroid; C038753:leptomycin B