Difference between revisions of "Phosphatase Subfamily STYXL1"

Revision as of 21:58, 12 May 2015

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily STYXL1

STYXL1 (MK-STYX) is a pseudophosphatase (catalytically inactive) conserved in metazoan but lost in ecdysozoan. Two binding partners have been known so far: phosphatase PTPMT1 and a Ras signaling regulator G3BP1.

Evolution

STYXL1 is found in metazoa but lost in ecdysozoa (arthropoda and nematoda). It is usually a copy per genome.

Domain

STYXL1 has two domains, N-terminal rhodanese domain and C-terminal phosphatase domain.

Function

STYXL1 is expressed in most tissues (see GTEx data).

STYXL1 physically and genetically interacts with the mitochondrial phosphatase PTPMT1, and suppresses PTPMT1 catalytic activity. STYXL1 knockdown induces robust chemoresistance to multiple cytotoxic death-inducing agents. Loss of STYXL1 blocks cytochrome c release, a critical and rate-limiting step in apoptosis. knockdown of PTPMT1 resensitizes STYXL1 knockdown cells to chemotherapeutics and restores the ability to release cytochrome c. Thus, a model has been proposed that MK-STYX controls apoptosis by negatively regulating PTPMT1 [1, 2].

STYXL1 also interacts with G3BP-1 (Ras-GTPase activating protein SH3 domain binding protein-1), a key component of stress granules. G3BP1 is an RNA-binding protein with endoribonuclease activity that is recruited to 'stress granules' after stress stimuli. Stress granules are large subcellular structures that serve as sites of mRNA sorting, in which untranslated mRNAs accumulate. Active mutant STYXL1 (active) has opposite effects to wild-type STYKL1 (inactive). The mutant STYXL1 (active) induces stress granules and dephosphorylates G3BP-1. [3, 4].

References

1. Niemi NM, Lanning NJ, Klomp JA, Tait SW, Xu Y, Dykema KJ, Murphy LO, Gaither LA, Xu HE, Furge KA, Green DR, and MacKeigan JP. MK-STYX, a catalytically inactive phosphatase regulating mitochondrially dependent apoptosis. Mol Cell Biol. 2011 Apr;31(7):1357-68. DOI:10.1128/MCB.00788-10 | PubMed ID:21262771 | HubMed [Niemi11]
2. Niemi NM, Sacoman JL, Westrate LM, Gaither LA, Lanning NJ, Martin KR, and MacKeigan JP. The pseudophosphatase MK-STYX physically and genetically interacts with the mitochondrial phosphatase PTPMT1. PLoS One. 2014;9(4):e93896. DOI:10.1371/journal.pone.0093896 | PubMed ID:24709986 | HubMed [Niemi14]
3. Hinton SD, Myers MP, Roggero VR, Allison LA, and Tonks NK. The pseudophosphatase MK-STYX interacts with G3BP and decreases stress granule formation. Biochem J. 2010 Apr 14;427(3):349-57. DOI:10.1042/BJ20091383 | PubMed ID:20180778 | HubMed [Hinton10]
4. Barr JE, Munyikwa MR, Frazier EA, and Hinton SD. The pseudophosphatase MK-STYX inhibits stress granule assembly independently of Ser149 phosphorylation of G3BP-1. FEBS J. 2013 Jan;280(1):273-84. DOI:10.1111/febs.12068 | PubMed ID:23163895 | HubMed [Barr13]