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Latency of transcription factor Stp1 depends on a modular regulatory motif that functions as cytoplasmic retention determinant and nuclear degron.

Omnus DJ, Ljungdahl PO - Mol. Biol. Cell (2014)

Bottom Line: Stp1, the effector transcription factor, is synthesized as a latent cytoplasmic precursor with an N-terminal regulatory domain that restricts its nuclear accumulation.Our results indicate that RI mediates latency by two distinct activities: it functions as a cytoplasmic retention determinant and an Asi-dependent degron.These findings provide novel insights into the SPS-sensing pathway and demonstrate for the first time that the inner nuclear membrane Asi proteins function in a degradation pathway in the nucleus.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden.

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Related in: MedlinePlus

Model. Two functional activities intrinsic to the RI motif ensure Stp1 latency. (A) In wild-type cells growing in the absence of inducing amino acids, the RI motif functions as a cytoplasmic retention determinant due to its interaction with an unidentified cytoplasmic component (anchor) that associates with the plasma membrane. RI binding is not absolute; small amounts of Stp1 target the nucleus where Stp1 is degraded in an RI motif- and Asi-dependent manner. (B) In cells lacking any of the Asi proteins, the low levels of Stp1 that escape cytoplasmic anchoring can access and bind promoters of SPS sensor–regulated genes, leading to induction of amino acid permease (AAP) gene expression.
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Figure 8: Model. Two functional activities intrinsic to the RI motif ensure Stp1 latency. (A) In wild-type cells growing in the absence of inducing amino acids, the RI motif functions as a cytoplasmic retention determinant due to its interaction with an unidentified cytoplasmic component (anchor) that associates with the plasma membrane. RI binding is not absolute; small amounts of Stp1 target the nucleus where Stp1 is degraded in an RI motif- and Asi-dependent manner. (B) In cells lacking any of the Asi proteins, the low levels of Stp1 that escape cytoplasmic anchoring can access and bind promoters of SPS sensor–regulated genes, leading to induction of amino acid permease (AAP) gene expression.

Mentions: The RI-mediated mechanisms defined in this work and schematically presented in Figure 8 fully account for the latent properties of Stp1. Accordingly, RI retains the bulk of Stp1 in the cytoplasm, presumably by interacting with a cytoplasmically exposed protein determinant (Figure 8A; anchor). However, due to the noncovalent nature of protein–protein interactions, cytoplasmic anchoring is not absolute. Hence small amounts of full-length Stp1 possessing the RI motif constitutively escape anchoring and inappropriately enter the nucleus. In the nucleus, the integral inner nuclear membrane Asi proteins function in concert to effectively target the unprocessed Stp1 for degradation and thereby prevent Stp1 from binding SPS sensor–regulated promoters. Consequently, in cells lacking any of the Asi proteins, the small pool of Stp1 that enters the nucleus is not effectively degraded, leading to induced gene expression (Figure 8B).


Latency of transcription factor Stp1 depends on a modular regulatory motif that functions as cytoplasmic retention determinant and nuclear degron.

Omnus DJ, Ljungdahl PO - Mol. Biol. Cell (2014)

Model. Two functional activities intrinsic to the RI motif ensure Stp1 latency. (A) In wild-type cells growing in the absence of inducing amino acids, the RI motif functions as a cytoplasmic retention determinant due to its interaction with an unidentified cytoplasmic component (anchor) that associates with the plasma membrane. RI binding is not absolute; small amounts of Stp1 target the nucleus where Stp1 is degraded in an RI motif- and Asi-dependent manner. (B) In cells lacking any of the Asi proteins, the low levels of Stp1 that escape cytoplasmic anchoring can access and bind promoters of SPS sensor–regulated genes, leading to induction of amino acid permease (AAP) gene expression.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 8: Model. Two functional activities intrinsic to the RI motif ensure Stp1 latency. (A) In wild-type cells growing in the absence of inducing amino acids, the RI motif functions as a cytoplasmic retention determinant due to its interaction with an unidentified cytoplasmic component (anchor) that associates with the plasma membrane. RI binding is not absolute; small amounts of Stp1 target the nucleus where Stp1 is degraded in an RI motif- and Asi-dependent manner. (B) In cells lacking any of the Asi proteins, the low levels of Stp1 that escape cytoplasmic anchoring can access and bind promoters of SPS sensor–regulated genes, leading to induction of amino acid permease (AAP) gene expression.
Mentions: The RI-mediated mechanisms defined in this work and schematically presented in Figure 8 fully account for the latent properties of Stp1. Accordingly, RI retains the bulk of Stp1 in the cytoplasm, presumably by interacting with a cytoplasmically exposed protein determinant (Figure 8A; anchor). However, due to the noncovalent nature of protein–protein interactions, cytoplasmic anchoring is not absolute. Hence small amounts of full-length Stp1 possessing the RI motif constitutively escape anchoring and inappropriately enter the nucleus. In the nucleus, the integral inner nuclear membrane Asi proteins function in concert to effectively target the unprocessed Stp1 for degradation and thereby prevent Stp1 from binding SPS sensor–regulated promoters. Consequently, in cells lacking any of the Asi proteins, the small pool of Stp1 that enters the nucleus is not effectively degraded, leading to induced gene expression (Figure 8B).

Bottom Line: Stp1, the effector transcription factor, is synthesized as a latent cytoplasmic precursor with an N-terminal regulatory domain that restricts its nuclear accumulation.Our results indicate that RI mediates latency by two distinct activities: it functions as a cytoplasmic retention determinant and an Asi-dependent degron.These findings provide novel insights into the SPS-sensing pathway and demonstrate for the first time that the inner nuclear membrane Asi proteins function in a degradation pathway in the nucleus.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden.

Show MeSH
Related in: MedlinePlus