Int J Biochem Mol Biol 2010;1(1):26-35
Review Article
Angiogenin-mediated rRNA transcription in cancer and neurodegeneration
Shuping Li and Guo-fu Hu
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, MA 02115
Received April 2, 2010; accepted May 5, 2010; available online May 15, 2010; published August 1, 2010
Abstract: Angiogenin (ANG) is a 14 kDa angiogenic ribonuclease that is upregulated in a variety of human cancers. Accumulating evidence
indicates that the angiogenic activity of ANG is related to its ability in regulating ribosomal RNA (rRNA) transcription. ANG is translocated to the
nucleus of growth-stimulated endothelial cells where it accumulates in the nucleolus, binds to the promoter region of ribosomal DNA (rDNA),
and stimulates rRNA transcription. This normally well-controlled process of nuclear translocation of ANG is hijacked by cancer cells that
constitutively uptake ANG and translocate it into the nucleus so that rRNA is constantly transcribed to meet a higher metabolic requirement of
this cells. Nuclear translocation of ANG therefore controls the rate of rRNA transcription and has been shown to be a molecular target for
cancer drug development. Recently, ANG has also been shown to play a role in motor neuron physiology. Loss-of-function mutations in the
coding region of ANG gene have been found in patients with amyotrophic lateral sclerosis (ALS). A deficiency in ANG function may result in
insufficient rRNA transcription in motor neurons that require robust ribosome biogenesis due to the demand of long axonal transport.
Haploinsufficiency of ANG has thus been implicated in ALS pathogenesis, and ANG has been shown to promote motor neuron survival both in
vitro and in vivo. Promotion of ANG expression or activity has been recognized as a therapeutic opportunity for ALS treatment. (IJBMB1004001).
Keywords: Angiogenin, ANG, rRNA transcription, cancer, neurodegeneration, rDNA, amyotrophic lateral sclerosis, ALS
Full Text PDF
Address all correspondence to:
Guo-Fu Hu, PhD,
Department of Pathology, Harvard Medical School
77 Avenue Louis Pasteur, MA 02115, USA.
E-mail: guofu_hu@hms.harvard.edu
Review Article
Angiogenin-mediated rRNA transcription in cancer and neurodegeneration
Shuping Li and Guo-fu Hu
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, MA 02115
Received April 2, 2010; accepted May 5, 2010; available online May 15, 2010; published August 1, 2010
Abstract: Angiogenin (ANG) is a 14 kDa angiogenic ribonuclease that is upregulated in a variety of human cancers. Accumulating evidence
indicates that the angiogenic activity of ANG is related to its ability in regulating ribosomal RNA (rRNA) transcription. ANG is translocated to the
nucleus of growth-stimulated endothelial cells where it accumulates in the nucleolus, binds to the promoter region of ribosomal DNA (rDNA),
and stimulates rRNA transcription. This normally well-controlled process of nuclear translocation of ANG is hijacked by cancer cells that
constitutively uptake ANG and translocate it into the nucleus so that rRNA is constantly transcribed to meet a higher metabolic requirement of
this cells. Nuclear translocation of ANG therefore controls the rate of rRNA transcription and has been shown to be a molecular target for
cancer drug development. Recently, ANG has also been shown to play a role in motor neuron physiology. Loss-of-function mutations in the
coding region of ANG gene have been found in patients with amyotrophic lateral sclerosis (ALS). A deficiency in ANG function may result in
insufficient rRNA transcription in motor neurons that require robust ribosome biogenesis due to the demand of long axonal transport.
Haploinsufficiency of ANG has thus been implicated in ALS pathogenesis, and ANG has been shown to promote motor neuron survival both in
vitro and in vivo. Promotion of ANG expression or activity has been recognized as a therapeutic opportunity for ALS treatment. (IJBMB1004001).
Keywords: Angiogenin, ANG, rRNA transcription, cancer, neurodegeneration, rDNA, amyotrophic lateral sclerosis, ALS
Full Text PDF
Address all correspondence to:
Guo-Fu Hu, PhD,
Department of Pathology, Harvard Medical School
77 Avenue Louis Pasteur, MA 02115, USA.
E-mail: guofu_hu@hms.harvard.edu
 |  |  |  |  |  |  |