Functional activity of RLIM/Rnf12 is regulated by phosphorylation-dependent nucleocytoplasmic shuttling |
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| Authors: | Baowei Jiao Naoko Taniguchi-Ishigaki Cenap Güng?r Marvin A Peters Ya-Wen Chen Sabine Riethdorf Alexander Drung Leanne G Ahronian JongDae Shin Rachna Pagnis Klaus Pantel Taro Tachibana Brian C Lewis Steven A Johnsen Ingolf Bach |
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| Institution: | Technical University Dresden;aProgram in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605-2324;dProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605-2324;bCentre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;cInstitute for Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany |
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| Abstract: | The X-linked gene Rnf12 encodes the ubiquitin ligase really interesting new gene (RING) finger LIM domain–interacting protein (RLIM)/RING finger protein 12 (Rnf12), which serves as a major sex-specific epigenetic regulator of female mouse nurturing tissues. Early during embryogenesis, RLIM/Rnf12 expressed from the maternal allele is crucial for the development of extraembryonic trophoblast cells. In contrast, in mammary glands of pregnant and lactating adult females RLIM/Rnf12 expressed from the paternal allele functions as a critical survival factor for milk-producing alveolar cells. Although RLIM/Rnf12 is detected mostly in the nucleus, little is known about how and in which cellular compartment(s) RLIM/Rnf12 mediates its biological functions. Here we demonstrate that RLIM/Rnf12 protein shuttles between nucleus and cytoplasm and this is regulated by phosphorylation of serine S214 located within its nuclear localization sequence. We show that shuttling is important for RLIM to exert its biological functions, as alveolar cell survival activity is inhibited in cells expressing shuttling-deficient nuclear or cytoplasmic RLIM/Rnf12. Thus regulated nucleocytoplasmic shuttling of RLIM/Rnf12 coordinates cellular compartments during mammary alveolar cell survival. |
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