A proteomic comparison of immature and mature mouse gonadotrophs reveals novel differentially expressed nuclear proteins that regulate gonadotropin gene transcription and RNA splicing.
A proteomic comparison of immature and mature mouse gonadotrophs reveals novel differentially expressed nuclear proteins that regulate gonadotropin gene transcription and RNA splicing.
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DOI:
10.1095/biolreprod.108.068106
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发表时间:
2008-09
影响因子:
3.6
通讯作者:
Melamed P
中科院分区:
文献类型:
--
作者:
Feng J;Lawson MA;Melamed P
The αT3-1 and LβT2 gonadotroph cell lines contain all the known factors required for expression of gonadotropin genes, yet only the LβT2 cells express the β-subunits. We hypothesized that comparison of their nuclear proteomes would reveal novel proteins and/or modifications that regulate expression of these genes. We identified nine proteins with different expression profiles in the two cell lines, of which several were chosen for further functional studies. Of those found at higher levels in αT3-1 nuclei, 1110005A23RIK was found associated with the Fshb gene promoter and repressed its expression; TAGLN3 over-expression reduced transcript levels of Fshb, and its knockdown elevated Lhb and Cga transcript levels, indicating an on-going repressive effect on these more highly expressed genes, possibly through altering levels of phosphorylated MAPK; HNRNPA2B1 repressed splicing of the Fshb primary transcript, which it binds in the first intron. Proteins at higher levels in LβT2 nuclei included prohibitin, whose over-expression reduced promoter activity of all three gonadotropin subunits and appeared to mediate the differential effect of GnRH on proliferation of the two cell lines; its knockdown also altered cell morphology. Two other splicing factors were also found at higher levels in LβT2 nuclei: the knockdown of PRPF19 or EIF4A3 decreased splicing of Lhb, or of both β-subunit transcripts, respectively. The levels of Eif4a3 mRNA were increased by activin and both factors increased Fshb splicing. This study has revealed a number of novel factors that alter gonadotropin expression and gonadotroph function, and likely mediate or moderate effects of the regulatory hormones.
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影响因子:
4.8
作者:
Hutchison, S;LeBel, C;Chabot, B
通讯作者:
Chabot, B
影响因子:
3.3
作者:
Fu, YP;Liu, HW;Solway, J
通讯作者:
Solway, J
DOI:
10.1152/ajpheart.00306.2003
发表时间:
2003-10-01
影响因子:
4.8
作者:
Kaplan-Albuquerque, N;Garat, C;Nemenoff, RA
通讯作者:
Nemenoff, RA
影响因子:
16.8
作者:
Ballut, L;Marchadier, B;Le Hir, H
通讯作者:
Le Hir, H
DOI:
10.1073/pnas.0400933101
发表时间:
2004-03-23
影响因子:
11.1
作者:
Ferraiuolo, MA;Lee, CS;Sonenberg, N
通讯作者:
Sonenberg, N