Saritas Erdogan Sinem, Yilmaz Ahmet Erdal, Kumbasar Asli
Department of Molecular Biology and Genetics, Istanbul Technical University, Turkey.
FEBS Lett. 2024 Dec;598(23):2910-2925. doi: 10.1002/1873-3468.15010. Epub 2024 Sep 8.
NFIB is a transcription factor of the Nuclear Factor One (NFI) family that is essential for embryonic development. Post-translational control of NFIB or its upstream regulators have not been well characterized. Here, we show that PIN1 binds NFIB in a phosphorylation-dependent manner, via its WW domain. PIN1 interacts with the well-conserved N-terminal domains of all NFIs. Moreover, PIN1 attenuates the transcriptional activity of NFIB; this attenuation requires substrate binding by PIN1 but not its isomerase activity. Paradoxically, we found stabilization of NFIB by PIN1. We propose that PIN1 represses NFIB function not by regulating its abundance but by inducing a conformational change. These results identify NFIB as a novel PIN1 target and posit a role for PIN1 in post-translational regulation of NFIB and other NFIs.
NFIB是核因子一（NFI）家族的一种转录因子，对胚胎发育至关重要。NFIB或其上游调节因子的翻译后调控尚未得到充分表征。在此，我们表明PIN1通过其WW结构域以磷酸化依赖的方式与NFIB结合。PIN1与所有NFI高度保守的N端结构域相互作用。此外，PIN1减弱了NFIB的转录活性；这种减弱需要PIN1与底物结合，而不是其异构酶活性。矛盾的是，我们发现PIN1使NFIB稳定。我们提出，PIN1不是通过调节NFIB的丰度，而是通过诱导构象变化来抑制其功能。这些结果确定NFIB是一种新的PIN1靶点，并揭示了PIN1在NFIB和其他NFI翻译后调控中的作用。
