Int J Biochem Mol Biol 2012;3(2):137-151
Review Article
The CRM1 nuclear export protein in normal development and disease
Kevin T Nguyen, Michael P Holloway, Rachel A Altura
Department of Pediatrics, Division of Pediatric Hematology-Oncology, Hasbro Children’s Hospital and The Warren Alpert Medical School at
Brown University, Providence, Rhode Island, USA
Received April 12, 2012; accepted May 16, 2012; Epub May 18, 2012; Published June 15, 2012
Abstract: CRM1 (Chromosomal Maintenance 1, also known as Exportin 1) is the major mammalian export protein that facilitates the transport
of large macromolecules including RNA and protein across the nuclear membrane to the cytoplasm. The gene encoding CRM1 was originally
identified in yeast as required to maintain higher order chromosome structure. In mammalian cells, CRM1 was found to bind several nuclear
pore proteins hence its role in nuclear-cytosolic transport was discovered. In addition to nuclear-cytosolic transport, CRM1 also plays a role in
centrosome duplication and spindle assembly, especially in response to DNA damage. The crystal structure of CRM1 suggests a complex
protein that binds the Ran protein bound to GTP, allowing for a conformational change that facilitates binding to different cargo proteins through
a nuclear export signal (NES). Included in the cadre of cargo are multiple tumor suppressor and oncoproteins as p53, BRCA1, Survivin, NPM,
and APC, which function in the nucleus to regulate transcription or aid in chromosomal assembly and movement. An imbalance in the
cytosolic level of these proteins has been observed in cancer cells, resulting in either inactivation (tumor suppressor) or an excess of anti-
apoptotic activity (oncoprotein). Thus, the concept of inhibiting CRM1 has been explored as a potential therapeutic intervention. Indeed,
inhibition of CRM1 by a variety of small molecules that interfere with cargo-NES binding results in cancer cell death. Whether all of these
proteins together are responsible for this phenotype or whether specific proteins are required for this effect is unclear at this time.
(IJBMB1204001).
Keywords: CRM1, nuclear pore complex, leptomycin B, p53, Survivin, APC, p27, NPM, BRCA1
Address all correspondence to:
Dr. Rachel A Altura
Department of Pediatrics
Hasbro Children’s Hospital
593 Eddy Street, Providence RI 02903, USA.
E-mail: rachel_altura@brown.edu
Review Article
The CRM1 nuclear export protein in normal development and disease
Kevin T Nguyen, Michael P Holloway, Rachel A Altura
Department of Pediatrics, Division of Pediatric Hematology-Oncology, Hasbro Children’s Hospital and The Warren Alpert Medical School at
Brown University, Providence, Rhode Island, USA
Received April 12, 2012; accepted May 16, 2012; Epub May 18, 2012; Published June 15, 2012
Abstract: CRM1 (Chromosomal Maintenance 1, also known as Exportin 1) is the major mammalian export protein that facilitates the transport
of large macromolecules including RNA and protein across the nuclear membrane to the cytoplasm. The gene encoding CRM1 was originally
identified in yeast as required to maintain higher order chromosome structure. In mammalian cells, CRM1 was found to bind several nuclear
pore proteins hence its role in nuclear-cytosolic transport was discovered. In addition to nuclear-cytosolic transport, CRM1 also plays a role in
centrosome duplication and spindle assembly, especially in response to DNA damage. The crystal structure of CRM1 suggests a complex
protein that binds the Ran protein bound to GTP, allowing for a conformational change that facilitates binding to different cargo proteins through
a nuclear export signal (NES). Included in the cadre of cargo are multiple tumor suppressor and oncoproteins as p53, BRCA1, Survivin, NPM,
and APC, which function in the nucleus to regulate transcription or aid in chromosomal assembly and movement. An imbalance in the
cytosolic level of these proteins has been observed in cancer cells, resulting in either inactivation (tumor suppressor) or an excess of anti-
apoptotic activity (oncoprotein). Thus, the concept of inhibiting CRM1 has been explored as a potential therapeutic intervention. Indeed,
inhibition of CRM1 by a variety of small molecules that interfere with cargo-NES binding results in cancer cell death. Whether all of these
proteins together are responsible for this phenotype or whether specific proteins are required for this effect is unclear at this time.
(IJBMB1204001).
Keywords: CRM1, nuclear pore complex, leptomycin B, p53, Survivin, APC, p27, NPM, BRCA1
Address all correspondence to:
Dr. Rachel A Altura
Department of Pediatrics
Hasbro Children’s Hospital
593 Eddy Street, Providence RI 02903, USA.
E-mail: rachel_altura@brown.edu
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