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DLC-1:a Rho GTPase-activating protein and tumour suppressor.

Durkin ME, Yuan BZ, Zhou X, Zimonjic DB, Lowy DR, Thorgeirsson SS, Popescu NC - J. Cell. Mol. Med. (2007 Sep-Oct)

Bottom Line: Since its discovery, compelling evidence has accumulated that demonstrates a role for DLC-1 as a bona fide tumour suppressor gene in different types of human cancer.Loss of DLC-1 expression mediated by genetic and epigenetic mechanisms has been associated with the development of many human cancers, and restoration of DLC-1 expression inhibited the growth of tumour cells in vivo and in vitro.Two closely related genes, DLC-2 and DLC-3, may also be tumour suppressors.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

ABSTRACT
The deleted in liver cancer 1 (DLC-1) gene encodes a GTPase activating protein that acts as a negative regulator of the Rho family of small GTPases. Rho proteins transduce signals that influence cell morphology and physiology, and their aberrant up-regulation is a key factor in the neoplastic process, including metastasis. Since its discovery, compelling evidence has accumulated that demonstrates a role for DLC-1 as a bona fide tumour suppressor gene in different types of human cancer. Loss of DLC-1 expression mediated by genetic and epigenetic mechanisms has been associated with the development of many human cancers, and restoration of DLC-1 expression inhibited the growth of tumour cells in vivo and in vitro. Two closely related genes, DLC-2 and DLC-3, may also be tumour suppressors. This review presents the current status of progress in understanding the biological functions of DLC-1 and its relatives and their roles in neoplasia.

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Related in: MedlinePlus

Comparison of the mammalian and Drosophila DLC family proteins. Schematic representation of the structure of human DLC-1, DLC-2α and DLC-3α, the rat DLC-1 orthologue p122RhoGAP and Drosophila RhoGAP88 C (cv-c). The SAM, serine-rich (SR), RhoGAP and START domains are indicated. The amino acid length of the polypeptide is given at the right. Beneath each domain is the percent identity to the corresponding domain of human DLC-1, and in parenthesis is the percent identity of the full-length polypeptide.
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fig02: Comparison of the mammalian and Drosophila DLC family proteins. Schematic representation of the structure of human DLC-1, DLC-2α and DLC-3α, the rat DLC-1 orthologue p122RhoGAP and Drosophila RhoGAP88 C (cv-c). The SAM, serine-rich (SR), RhoGAP and START domains are indicated. The amino acid length of the polypeptide is given at the right. Beneath each domain is the percent identity to the corresponding domain of human DLC-1, and in parenthesis is the percent identity of the full-length polypeptide.

Mentions: DLC-1 was later recognized as the founding member of a family of proteins that shares the SAM-RhoGAP-START domain organization, which now includes DLC-2 (also known as STARD13, for START domain-containing protein 13) [19, 20] and DLC-3 (also known as KIAA0189 and STARD8) [21, 22] (Fig. 2). The genes encoding the three human DLC proteins appear to be paralogues that arose through duplication of chromoso-mal segments [22]. Orthologues of each of the three DLC family proteins have been found in other vertebrates, including the mouse, rat, dog, chicken, frog and puffer fish (Ensembl Project; http://www.ensembl.org). The urochordate Ciona intestinalis and invertebrates such as Drosophila and C. elegans appear to possess a single gene encoding a DLC-1-like protein (Ensembl Project). The SAM-RhoGAP-START domain proteins apparently arose in multi-cellular organisms, as none of the 11 predicted RhoGAP domain proteins in S. cerevisiae is homologous to DLC-1 [23].


DLC-1:a Rho GTPase-activating protein and tumour suppressor.

Durkin ME, Yuan BZ, Zhou X, Zimonjic DB, Lowy DR, Thorgeirsson SS, Popescu NC - J. Cell. Mol. Med. (2007 Sep-Oct)

Comparison of the mammalian and Drosophila DLC family proteins. Schematic representation of the structure of human DLC-1, DLC-2α and DLC-3α, the rat DLC-1 orthologue p122RhoGAP and Drosophila RhoGAP88 C (cv-c). The SAM, serine-rich (SR), RhoGAP and START domains are indicated. The amino acid length of the polypeptide is given at the right. Beneath each domain is the percent identity to the corresponding domain of human DLC-1, and in parenthesis is the percent identity of the full-length polypeptide.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401278&req=5

fig02: Comparison of the mammalian and Drosophila DLC family proteins. Schematic representation of the structure of human DLC-1, DLC-2α and DLC-3α, the rat DLC-1 orthologue p122RhoGAP and Drosophila RhoGAP88 C (cv-c). The SAM, serine-rich (SR), RhoGAP and START domains are indicated. The amino acid length of the polypeptide is given at the right. Beneath each domain is the percent identity to the corresponding domain of human DLC-1, and in parenthesis is the percent identity of the full-length polypeptide.
Mentions: DLC-1 was later recognized as the founding member of a family of proteins that shares the SAM-RhoGAP-START domain organization, which now includes DLC-2 (also known as STARD13, for START domain-containing protein 13) [19, 20] and DLC-3 (also known as KIAA0189 and STARD8) [21, 22] (Fig. 2). The genes encoding the three human DLC proteins appear to be paralogues that arose through duplication of chromoso-mal segments [22]. Orthologues of each of the three DLC family proteins have been found in other vertebrates, including the mouse, rat, dog, chicken, frog and puffer fish (Ensembl Project; http://www.ensembl.org). The urochordate Ciona intestinalis and invertebrates such as Drosophila and C. elegans appear to possess a single gene encoding a DLC-1-like protein (Ensembl Project). The SAM-RhoGAP-START domain proteins apparently arose in multi-cellular organisms, as none of the 11 predicted RhoGAP domain proteins in S. cerevisiae is homologous to DLC-1 [23].

Bottom Line: Since its discovery, compelling evidence has accumulated that demonstrates a role for DLC-1 as a bona fide tumour suppressor gene in different types of human cancer.Loss of DLC-1 expression mediated by genetic and epigenetic mechanisms has been associated with the development of many human cancers, and restoration of DLC-1 expression inhibited the growth of tumour cells in vivo and in vitro.Two closely related genes, DLC-2 and DLC-3, may also be tumour suppressors.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

ABSTRACT
The deleted in liver cancer 1 (DLC-1) gene encodes a GTPase activating protein that acts as a negative regulator of the Rho family of small GTPases. Rho proteins transduce signals that influence cell morphology and physiology, and their aberrant up-regulation is a key factor in the neoplastic process, including metastasis. Since its discovery, compelling evidence has accumulated that demonstrates a role for DLC-1 as a bona fide tumour suppressor gene in different types of human cancer. Loss of DLC-1 expression mediated by genetic and epigenetic mechanisms has been associated with the development of many human cancers, and restoration of DLC-1 expression inhibited the growth of tumour cells in vivo and in vitro. Two closely related genes, DLC-2 and DLC-3, may also be tumour suppressors. This review presents the current status of progress in understanding the biological functions of DLC-1 and its relatives and their roles in neoplasia.

Show MeSH
Related in: MedlinePlus