Structure-Function Analysis of Core STRIPAK Proteins

Kean, Michelle J.; Ceccarelli, Derek F.; Goudreault, Marilyn; Sanches, Mário; Tate, Stephen; Larsen, Brett; Gibson, Lucien C.D.; Derry, W. Brent; Scott, Ian C.; Pelletier, Laurence; Baillie, George S.; Sicheri, Frank; Gingras, Anne‐Claude

doi:10.1074/jbc.m110.214486

Cited by 137 publications

(101 citation statements)

References 49 publications

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“…SETD6-associated peptides were affinity purified using an α-FLAG matrix. Then, SETD6-associated proteins were essentially identified by previously described mass spectrometric methods 24 , 25 . Interestingly, several SETD6-associated proteins identified have known biological functions related to nuclear hormone signaling (Fig.…”

Section: Resultsmentioning

confidence: 99%

SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells

O’Neill¹,

Williamson²,

Alkharaif³

et al. 2014

Epigenetics

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The lysine methyltransferase SETD6 modifies the histone variant H2AZ, a key component of nuclear receptor-dependent transcription. Herein, we report the identification of several factors that associate with SETD6 and are implicated in nuclear hormone receptor signaling. Specifically, SETD6 associates with the estrogen receptor α (ERα), histone deacetylase HDAC1, metastasis protein MTA2, and the transcriptional co-activator TRRAP. Luciferase reporter assays identify SETD6 as a transcriptional repressor, in agreement with its association with HDAC1 and MTA2. However, SETD6 behaves as a co-activator of several estrogen-responsive genes, such as PGR and TFF1. Consistent with these results, silencing of SETD6 in several breast carcinoma cell lines induced cellular proliferation defects accompanied by enhanced expression of the cell cycle inhibitor CDKN1A and induction of apoptosis. Herein, we have identified several chromatin proteins that associate with SETD6 and described SETD6 as an essential factor for nuclear receptor signaling and cellular proliferation.

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Section: Resultsmentioning

confidence: 99%

SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells

O’Neill¹,

Williamson²,

Alkharaif³

et al. 2014

Epigenetics

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“…The high diversity of STRIPAK and STRIPAKlike complexes makes estimation of the molecular weight of the complex difficult. Human STRIPAK was found to play a role in Golgi apparatus polarization and is involved in mitosis by tether-ing Golgi vesicles to centrosomes and the nuclear membrane in a cell cycle-specific manner (22,23).…”

mentioning

confidence: 99%

A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria

et al. 2015

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bSarcolemmal membrane-associated protein (SLMAP) is a tail-anchored protein involved in fundamental cellular processes, such as myoblast fusion, cell cycle progression, and chromosomal inheritance. Further, SLMAP misexpression is associated with endothelial dysfunctions in diabetes and cancer. SLMAP is part of the conserved striatin-interacting phosphatase and kinase (STRIPAK) complex required for specific signaling pathways in yeasts, filamentous fungi, insects, and mammals. In filamentous fungi, STRIPAK was initially discovered in Sordaria macrospora, a model system for fungal differentiation. Here, we functionally characterize the STRIPAK subunit PRO45, a homolog of human SLMAP. We show that PRO45 is required for sexual propagation and cell-to-cell fusion and that its forkhead-associated (FHA) domain is essential for these processes. Protein-protein interaction studies revealed that PRO45 binds to STRIPAK subunits PRO11 and SmMOB3, which are also required for sexual propagation. Superresolution structured-illumination microscopy (SIM) further established that PRO45 localizes to the nuclear envelope, endoplasmic reticulum, and mitochondria. SIM also showed that localization to the nuclear envelope requires STRIPAK subunits PRO11 and PRO22, whereas for mitochondria it does not. Taken together, our study provides important insights into fundamental roles of the fungal SLMAP homolog PRO45 and suggests STRIPAK-related and STRIPAK-unrelated functions. Membrane recruitment of protein complexes, cell signaling modules, and enzymes is a critical step for many cellular functions. The family of tail-anchored proteins is recognized for anchoring proteins and vesicles to specific membranes, such as the endoplasmic reticulum (ER) and the outer mitochondrial membrane (1), and tail-anchored proteins are characterized by a C-terminal single transmembrane domain, which is posttranslationally inserted into membranes (2, 3).Sarcolemmal membrane-associated protein (SLMAP) is a tailanchored protein first identified in myocardiac cells (4). In mammals, this protein is known to be involved in myoblast fusion during embryonic development, excitation-contraction coupling in cardiac myocytes, and cell cycle progression (5-8). Furthermore, SLMAP was identified to be a disease gene for Brugada syndrome, a cardiac channelopathy (9). The functional diversity of SLMAP is dependent on alternative splicing, leading to at least four different isoforms of the protein (4, 6, 7, 10). Importantly, gene expression analyses have implicated SLMAP misexpression with endothelial dysfunctions in diabetes, chromosomal aberrations, and cancer (11-14), and currently, SLMAP is the target of lectin-based treatment of drug-resistant cancer cells (15).SLMAP is conserved from yeasts to humans, and characterized fungal SLMAP homologs include Neurospora crassa HAM-4 (hyphal anastomosis 4), Saccharomyces cerevisiae Far9p (factor arrest 9p) and Far10p, as well as Schizosaccharomyces pombe Csc1p (component of SIP complex 1p) (16-18). HAM-4 is essential for vegetativ...

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“…Since HSP90 is one of the proteins most frequently detected in our standard AP-MS protocol, it would certainly have been filtered out by binary filters; however, when a newly developed tool called SAINT (Significance Analysis of INTeractome) [47], was applied, we were able to model the spectral count distribution for HSP90 (and all other proteins in the samples) across negative control samples, and provide a confidence value for each of the putative interactions detected. In addition to SAINT which has now been applied to large [15,69] and small [27,54] datasets and to intensity-based quantification [70], similar software tools that use label-free information to score the quality of protein-protein interactions have been developed [45,46,71]. All these tools were demonstrated to provide a more rigorous filtering of the contaminants than simple filters, leading to a better recovery of true interacting partners, though which tool performs best is dependent on the dataset at hand.…”

Section: From Identification and Relative Quantification To Interactionmentioning

confidence: 99%

“…In this case, the differential quantification between two or more samples is analyzed independently with sequential LC-MS runs, and software tools are used to calculate the relative area under the chromatographic peak. MS1-based quantification, when performed carefully, has proven very useful for the analysis of affinity-purified samples [52][53][54]. In addition to MS1-based quantification, another technique that is gaining increasing popularity is selected reaction monitoring (SRM).…”

Section: Quantitative Mass Spectrometrymentioning

confidence: 99%

Mass spectrometry approaches to study mammalian kinase and phosphatase associated proteins

Kean

Couzens

Gingras

2012

Methods

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Structure-Function Analysis of Core STRIPAK Proteins

Cited by 137 publications

References 49 publications

SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells

SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells

A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria

Mass spectrometry approaches to study mammalian kinase and phosphatase associated proteins

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