TY - JOUR
T1 - Identification of dAven, a Drosophila melanogaster ortholog of the cell cycle regulator Aven
T2 - Identification of Drosophila Aven
AU - Zou, Sige
AU - Chang, Joy
AU - LaFever, Leesa
AU - Tang, Wangli
AU - Johnson, Erika L.
AU - Hu, Jack
AU - Wilk, Ronit
AU - Krause, Henry M.
AU - Drummond-Barbosa, Daniela
AU - Irusta, Pablo M.
N1 - Funding Information:
This work was supported by Fundacion INFANT (PI), R01 GM069875 (DDB), and Intramural Research Program of the National Institute on Aging, NIH (SZ). LL designed and performed experiments in Figure 4 under the guidance of DDB. The authors would like to thank Sheryl Southard and Mark Van Doren from Johns Hopkins University for their help with some experiments performed during the course of this project.
PY - 2011/3/15
Y1 - 2011/3/15
N2 - Aven is a regulator of the DNA damage response and G2/M cell cycle progression. Overexpression of Aven is associated with poor prognosis in patients with childhood acute lymphoblastic leukemia and acute myeloid leukemia, and altered intracellular Aven distribution is associated with infiltrating ductal carcinoma and papillary carcinoma breast cancer subtypes. Although Aven orthologs have been identified in most vertebrate species, no Aven gene has been reported in invertebrates. Here, we describe a Drosophila melanogaster open reading frame (ORF) that shares sequence and functional similarities with vertebrate Aven genes. The protein encoded by this ORF, which we named dAven, contains several domains that are highly conserved among Aven proteins of fish, amphibian, bird and mammalian origins. In flies, knockdown of dAven by RNA interference (RNAi) resulted in lethality when its expression was reduced either ubiquitously or in fat cells using Gal4 drivers. Animals undergoing moderate dAven knockdown in the fat body had smaller fat cells displaying condensed chromosomes and increased levels of the mitotic marker phosphorylated histone H3 (PHH3), suggesting that dAven was required for normal cell cycle progression in this tissue. Remarkably, expression of dAven in Xenopus egg extracts resulted in G2/M arrest that was comparable to that caused by human Aven. Taken together, these results suggest that, like its vertebrate counterparts, dAven plays a role in cell cycle regulation. Drosophila could be an excellent model for studying the function of Aven and identifying cellular factors that influence its activity, revealing information that may be relevant to human disease.
AB - Aven is a regulator of the DNA damage response and G2/M cell cycle progression. Overexpression of Aven is associated with poor prognosis in patients with childhood acute lymphoblastic leukemia and acute myeloid leukemia, and altered intracellular Aven distribution is associated with infiltrating ductal carcinoma and papillary carcinoma breast cancer subtypes. Although Aven orthologs have been identified in most vertebrate species, no Aven gene has been reported in invertebrates. Here, we describe a Drosophila melanogaster open reading frame (ORF) that shares sequence and functional similarities with vertebrate Aven genes. The protein encoded by this ORF, which we named dAven, contains several domains that are highly conserved among Aven proteins of fish, amphibian, bird and mammalian origins. In flies, knockdown of dAven by RNA interference (RNAi) resulted in lethality when its expression was reduced either ubiquitously or in fat cells using Gal4 drivers. Animals undergoing moderate dAven knockdown in the fat body had smaller fat cells displaying condensed chromosomes and increased levels of the mitotic marker phosphorylated histone H3 (PHH3), suggesting that dAven was required for normal cell cycle progression in this tissue. Remarkably, expression of dAven in Xenopus egg extracts resulted in G2/M arrest that was comparable to that caused by human Aven. Taken together, these results suggest that, like its vertebrate counterparts, dAven plays a role in cell cycle regulation. Drosophila could be an excellent model for studying the function of Aven and identifying cellular factors that influence its activity, revealing information that may be relevant to human disease.
KW - ATM and Rad 3-related
KW - Ataxia telangiectasia mutated
KW - Aven
KW - Cell cycle
KW - Checkpoint
KW - Drosophila melanogaster
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U2 - 10.4161/cc.10.6.15080
DO - 10.4161/cc.10.6.15080
M3 - Article
C2 - 21368576
AN - SCOPUS:79952662479
SN - 1538-4101
VL - 10
SP - 989
EP - 998
JO - Cell Cycle
JF - Cell Cycle
IS - 6
ER -