Functional activity of RLIM/Rnf12 is regulated by phosphorylation-dependent nucleocytoplasmic shuttling
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Functional activity of RLIM/Rnf12 is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. / Jiao, Baowei; Taniguchi-Ishigaki, Naoko; Güngör, Cenap; Peters, Marvin A; Chen, Ya-Wen; Riethdorf, Sabine; Drung, Alexander; Ahronian, Leanne G; Shin, Jongdae; Pagnis, Rachna; Pantel, Klaus; Tachibana, Taro; Lewis, Brian C; Johnsen, Steven A; Bach, Ingolf.
in: MOL BIOL CELL, Jahrgang 24, Nr. 19, 01.10.2013, S. 3085-96.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Functional activity of RLIM/Rnf12 is regulated by phosphorylation-dependent nucleocytoplasmic shuttling
AU - Jiao, Baowei
AU - Taniguchi-Ishigaki, Naoko
AU - Güngör, Cenap
AU - Peters, Marvin A
AU - Chen, Ya-Wen
AU - Riethdorf, Sabine
AU - Drung, Alexander
AU - Ahronian, Leanne G
AU - Shin, Jongdae
AU - Pagnis, Rachna
AU - Pantel, Klaus
AU - Tachibana, Taro
AU - Lewis, Brian C
AU - Johnsen, Steven A
AU - Bach, Ingolf
PY - 2013/10/1
Y1 - 2013/10/1
N2 - 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.
AB - 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.
KW - Active Transport, Cell Nucleus
KW - Animals
KW - Cell Nucleus
KW - Cell Survival
KW - Embryonic Development
KW - Epigenesis, Genetic
KW - Female
KW - HeLa Cells
KW - Humans
KW - LIM Domain Proteins
KW - Mammary Glands, Animal
KW - Mice
KW - Phosphorylation
KW - Pregnancy
KW - Sex Determination Processes
KW - Ubiquitin-Protein Ligases
U2 - 10.1091/mbc.E13-05-0239
DO - 10.1091/mbc.E13-05-0239
M3 - SCORING: Journal article
C2 - 23904271
VL - 24
SP - 3085
EP - 3096
JO - MOL BIOL CELL
JF - MOL BIOL CELL
SN - 1059-1524
IS - 19
ER -