C. elegans FOG-3/Tob can either promote or inhibit germline proliferation, depending on gene dosage and genetic context.
C. elegans FOG-3/Tob can either promote or inhibit germline proliferation, depending on gene dosage and genetic context.
复制标题
秀丽隐杆线虫FOG-3/TOB可以根据基因剂量和遗传环境促进或抑制种系增殖。
DOI：
10.1038/onc.2012.291
复制
发表时间：
2013-05-23
期刊：
影响因子：
8
通讯作者：
Kimble, J.
中科院分区：
文献类型：
--
作者：
Snow, J. J.;Lee, M-H;Verheyden, J.;Kroll-Conner, P. L.;Kimble, J.
Vertebrate Tob/BTG proteins inhibit cell proliferation when overexpressed in tissue culture cells, and they can function as tumor suppressors in mice. The single Caenorhabditis elegans Tob/BTG ortholog, FOG-3, by contrast, was identified from its loss-of-function phenotype as a regulator of sperm fate specification. Here we report that FOG-3 also regulates proliferation in the germline tissue. We first demonstrate that FOG-3 is a positive regulator of germline proliferation. Thus, fog-3 null mutants possess fewer germ cells than normal, a modest but reproducible decrease observed for each of two distinct fog-3 null alleles. A similar decrease also occurred in fog-3/+ heterozygotes, again for both fog-3 alleles, revealing a haplo-insufficient effect on proliferation. Therefore, FOG-3 normally promotes proliferation, and two copies of the fog-3 gene are required for this function. We next overexpressed FOG-3 by removal of FBF, the collective term for FBF-1 and FBF-2, two nearly identical PUF RNA-binding proteins. We find that overexpressed FOG-3 blocks proliferation in fbf-1 fbf-2 mutants: whereas germ cells stop dividing and instead differentiate in fbf-1 fbf-2 double mutants, they continue to proliferate in fog-3; fbf-1 fbf-2 triple mutants. Therefore, like its vertebrate Tob/BTG cousins, overexpressed FOG-3 is “antiproliferative”. Indeed, some fog-3; fbf-1 fbf-2 mutants possess small tumors, suggesting that FOG-3 can act as a tumor suppressor. Finally, we show that FOG-3 and FBF work together to promote tumor formation in animals carrying oncogenic Notch mutations. A similar effect was not observed when germline tumors were induced by manipulation of other regulators; therefore this FOG-3 tumor-promoting effect is context-dependent. We conclude that FOG-3 can either promote or inhibit proliferation in a manner that is sensitive to both genetic context and gene dosage. The discovery of these FOG-3 effects on proliferation has implications for our understanding of vertebrate Tob/BTG proteins and their influence on normal development and tumorigenesis.
登录
查看更多内容
影响因子：
9.7
作者：
Ito, Y;Suzuki, T;Miyauchi, A
通讯作者：
Miyauchi, A
影响因子：
4.7
作者：
Ficazzola, MA;Fraiman, M;Walden, PD
通讯作者：
Walden, PD
影响因子：
9.7
作者：
Iwanaga, K;Sueoka, N;Sueoka, E
通讯作者：
Sueoka, E
影响因子：
4.8
作者：
Farioli-Vecchioli, Stefano;Tanori, Mirella;Tirone, Felice
通讯作者：
Tirone, Felice
影响因子：
11.8
作者：
Lamont, LB;Crittenden, SL;Kimble, J
通讯作者：
Kimble, J