Located on the short arm of chromosome 3 (3p25-p26), the VHL
tumour suppressor gene was first identified and cloned in 1993
[16]. The gene, which contains 3 exons, encodes a protein of 213
amino acid residues, specifically known as pVHL30. A second
wild-type isoform of 160 amino acid residues is also expressed in
human cells. pVHL19 arises from alternate translation initiation at
a second AUG codon (codon 54) within the VHL open reading
frame [17]. Both forms are known to display tumour suppressor
abilities. Reintroduction of RCC cells with either pVHL19 or pVHL30
inhibits tumour development in mouse xenograft models of the
disease [18]. Although both are expressed in human cells, pVHL19
is often the more prominent form in human tissue. Interestingly
VHL isoforms are also located in different compartments of the cell.
While VHL19 is equally distributed in the nucleus and cytoplasm,
VHL30 is found predominantly in the cytoplasm [17], suggesting
that under certain circumstances they display distinct roles. However, for the remainder of this review, unless otherwise stated,both protein forms of VHL will be referred to as pVHL
Located on the short arm of chromosome 3 (3p25-p26), the VHLtumour suppressor gene was first identified and cloned in 1993[16]. The gene, which contains 3 exons, encodes a protein of 213amino acid residues, specifically known as pVHL30. A secondwild-type isoform of 160 amino acid residues is also expressed inhuman cells. pVHL19 arises from alternate translation initiation ata second AUG codon (codon 54) within the VHL open readingframe [17]. Both forms are known to display tumour suppressorabilities. Reintroduction of RCC cells with either pVHL19 or pVHL30inhibits tumour development in mouse xenograft models of thedisease [18]. Although both are expressed in human cells, pVHL19is often the more prominent form in human tissue. InterestinglyVHL isoforms are also located in different compartments of the cell.While VHL19 is equally distributed in the nucleus and cytoplasm,VHL30 is found predominantly in the cytoplasm [17], suggestingthat under certain circumstances they display distinct roles. However, for the remainder of this review, unless otherwise stated,both protein forms of VHL will be referred to as pVHL
การแปล กรุณารอสักครู่..
