Budde Lucy M, Wu Chun, Tilman Christopher, Douglas Iris, Ghosh Sankar
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Mol Biol Cell. 2002 Dec;13(12):4179-94. doi: 10.1091/mbc.01-07-0373.
IkappaBalpha and IkappaBbeta are regulators of the nuclear factor-kappaB (NF-kappaB) transcription factor family. Both IkappaBs bind to the same NF-kappaB dimers and are widely expressed in different cells and tissues. To better understand how these two IkappaB isoforms differ biologically, we have characterized the expression of IkappaBbeta in testis, a tissue in which IkappaBalpha is only minimally expressed. We have found that IkappaBbeta expression is localized within the haploid spermatid stages of spermatogenesis and follows the expression of nuclear NF-kappaB. IkappaBbeta expression in haploid spermatids is likely regulated by Sox family proteins, members of which are also expressed within spermatids. We have shown that both SRY and Sox-5 can bind to multiple Sox binding sites found within the IkappaBbeta promoter and can enhance transcription of a reporter gene in transient transfection assays. We also demonstrate that IkappaBbeta mRNA is strongly expressed in developing male gonads. These results therefore suggest that IkappaBbeta may be a novel target for transcription factors of the HMG-box SRY/Sox family and imply a potential role for NF-kappaB/IkappaBbeta in spermatogenesis.
IκBα和IκBβ是核因子-κB(NF-κB)转录因子家族的调节因子。两种IκB均与相同的NF-κB二聚体结合,并在不同细胞和组织中广泛表达。为了更好地理解这两种IκB同工型在生物学上的差异,我们对睾丸中IκBβ的表达进行了表征,睾丸是一种IκBα仅微量表达的组织。我们发现IκBβ的表达定位于精子发生的单倍体精子细胞阶段,并与核NF-κB的表达一致。单倍体精子细胞中IκBβ的表达可能受Sox家族蛋白调控,其中一些成员也在精子细胞中表达。我们已经表明,SRY和Sox-5均可与IκBβ启动子内发现的多个Sox结合位点结合,并在瞬时转染实验中增强报告基因的转录。我们还证明,IκBβ mRNA在发育中的雄性性腺中强烈表达。因此,这些结果表明IκBβ可能是HMG-box SRY/Sox家族转录因子的一个新靶点,并暗示NF-κB/IκBβ在精子发生中具有潜在作用。