Nucleocytoplasmic shuttling of the progesterone receptor.

Abstract

The nuclear localization of the progesterone receptor is mediated by two signal sequences: one is constitutive and lies in the hinge region (between the DNA and steroid binding domains), the other is hormone dependent and is localized in the second zinc finger of the DNA binding domain. The use of various inhibitors of energy synthesis in cells expressing permanently or transiently the wild‐type receptor or a receptor mutated within the nuclear localization signals, demonstrated that the nuclear residency of the receptor reflects a dynamic situation: the receptor diffusing into the cytoplasm and being constantly and actively transported back into the nucleus. The existence of this nucleo‐cytoplasmic shuttle mechanism was confirmed by receptor transfer from one nucleus to the other in heterokaryons. Preliminary evidence was obtained, using oestrogen receptor, that this phenomenon may be of general significance for steroid receptors.

Nuclear localization of liver X receptor α and β is differentially regulated

“…Another region that is important for nuclear localization (NLS2) is located in the second Zinc finger in the DNA binding domain of nuclear receptors such as orphan nuclear receptor TR2 [Yu et al, 1998] and PR [Guiochon-Mantel et al, 1991;Ylikomi et al, 1992]. Analogous sequences exist in the RXR as well as in LXR a and LXR b.…”

“…Export from the nucleus occurs through receptormediated mechanisms. Studies using heterokaryon and imaging experiments showed that exported nuclear receptors are reimported into the nucleus [Guiochon-Mantel et al, 1991;Hache et al, 1999;Prufer and Barsony, 2002]. It is well established that nuclear receptors are imported into the nucleus by karyopherins.…”

“…One amino acid within NLS1 is conserved among all type II nuclear receptors as either arginine or lysine. Basic amino acids in the second Zinc finger in the DBD of orphan nuclear receptor TR2 [Yu et al, 1998] and the PR [Guiochon-Mantel et al, 1991;Ylikomi et al, 1992] have also been shown to act as NLS (NLS2). Analogous amino acids in the second Zinc finger exist in other nuclear receptors such as RXR, LXR a, and LXR b.…”

“…Analogous amino acids in the second Zinc finger exist in other nuclear receptors such as RXR, LXR a, and LXR b. Another NLS (NLS3) has been identified in the hinge region of many nuclear receptors including PR [Guiochon-Mantel et al, 1991], ER [Ylikomi et al, 1992], GR [Picard and Yamamoto, 1987], AR [Zhou et al, 1994], the steroid and xenobiotic receptor (SXR) [Kawana et al, 2003], the mineralocorticoid receptor (MR) [Pearce et al, 2002], and the VDR [Luo et al, 1994]. Analogous regions exist in other nuclear receptors such as LXR a and LXR b, but not in RXR.…”

Vigilin contains a functional nuclear localisation sequence and is present in both the cytoplasm and the nucleus

“…Although specific nuclear export signals have been recently identified in a few proteins [27][28][29], there is also evidence arguing for nuclear export by a default pathway [30,31]. At present experimental evidence is lacking which could show whether Vigilin shuttles continuously across the nuclear envelope like some nucleolar proteins [32], the progesterone receptor [33] or some of the hnRNPs [27], or is stably anchored at the ER after it had passed by the nucleus.…”