Cross-talk between Remodeling and de Novo Pathways Maintains Phospholipid Balance through Ubiquitination

Butler, Phillip L.; Mallampalli, Rama K.

doi:10.1074/jbc.m109.017350

Cited by 35 publications

(27 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, this group contained multiple transmembrane proteins including some well characterized permeases and transporters such as the arginine transporter Can1 (Lys-42; 11-fold increase), the myo-inositol transporter Itr1 (Lys-41; 19-fold increase), the affinity methionine permease Mup1 (Lys-567; 3-fold increase), the lysine permease Lyp1 (Lys-54; 6-fold increase), and the high affinity copper transporter Ctr1 (Fig. 1C and supplemental Table 1) (7,33,34). The lysines modified by ubiquitin in PM proteins were exclusively located in the cytosolic loops of the proteins, and no structurally incoherent sites (located in intramembrane or extracellular loops) were identified.…”

Section: Resultsmentioning

confidence: 99%

Cold Temperature Induces the Reprogramming of Proteolytic Pathways in Yeast

Isasa

Suñer

Diaz

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Despite much evidence of the involvement of the proteasomeubiquitin signaling system in temperature stress response, the dynamics of the ubiquitylome during cold response has not yet been studied. Here, we have compared quantitative ubiquitylomes from a strain deficient in proteasome substrate recruitment and a reference strain during cold response. We have observed that a large group of proteins showing increased ubiquitylation in the proteasome mutant at low temperature is comprised by reverses suppressor of Ty-phenotype 5 (Rsp5)-regulated plasma membrane proteins. Analysis of internalization and degradation of plasma membrane proteins at low temperature showed that the proteasome becomes determinant for this process, whereas, at 30°C, the proteasome is dispensable. Moreover, our observations indicate that proteasomes have increased capacity to interact with lysine 63-polyubiquitylated proteins during low temperature in vivo. These unanticipated observations indicate that, during cold response, there is a proteolytic cellular reprogramming in which the proteasome acquires a role in the endocytic-vacuolar pathway.Proteasomal and endocytic-vacuolar pathways are responsible for the degradation of a large portion of proteins in eukaryotic cells, and their activities are fundamental for protein homeostasis. The endocytic-vacuolar pathway degrades internalized plasma membrane (PM) 3 proteins, proteins trafficking from Golgi to the endosome, and proteins from autophagic processes (1). The proteasome is the fate of cytosolic and nuclear proteins, co-translationally incomplete or misfolded proteins, partially aggregated proteins, and transmembrane proteins from the endoplasmic reticulum (2, 3). Despite the functional divergence between endocytic-vacuolar and proteasomal pathways, they share a key regulatory aspect: client proteins are modified by ubiquitin, and as a consequence ubiquitin-conjugating and ubiquitin-recognizing proteins act as receptors and regulators of both processes. The involvement of distinct ubiquitin-protein ligases, deubiquitylating factors, different polyubiquitin topologies, and specific recognition of ubiquitylated substrates appear to be key factors to ensure the independence of both pathways (1, 4, 5).In the initial steps of the endocytic pathway, yeast PM cargo proteins are mainly ubiquitylated by the Nedd4-type ubiquitin ligase Rsp5 (4, 6, 7). Ubiquitylated cargo proteins undergo endocytosis, a process orchestrated by epsins and epsin-like proteins, which possess two types of ubiquitin binding domains: ubiquitin-interacting motifs and ubiquitin-associated domains (8). Internalized proteins may exhibit monoubiquitylation or Lys-63-dependent polyubiquitylation (4, 7). In the endosome, ubiquitylated cargo is recruited to the ESCRT-0 complex constituted by Vps27 (Hrs) and Hse1 (STAM1/2). Both Vps27 and Hse1 proteins contain ubiquitin binding domains that mediate interaction with ubiquitylated cargo (9). During multivesicular body biogenesis, ubiquitin modification of cargo proteins is preserved...

show abstract

Section: Resultsmentioning

confidence: 99%

Cold Temperature Induces the Reprogramming of Proteolytic Pathways in Yeast

Isasa

Suñer

Diaz

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…35 l of H 2 O and cellular protein (10 g) was added to 10 l of sonicated assay buffer containing 5 l of [1-14 C]acyl-CoA (0.1 Ci, 1.8 nmol) for a total assay volume of 50 l. Upon addition of [1-14 C]acyl-CoA, samples were incubated at 30°C for 10 min, after which the reaction was terminated by addition of chloroform/methanol/H 2 O (1:2:0.70, v/v). Total cellular lipids from reaction mixtures were extracted by the method of Bligh and Dyer and spotted on LK5D plates, and PtdCho was resolved using TLC and detected using a Bioscan AR-2000 scintillation plate reader (7). Immunoprecipitation and Immunoblot Analysis-Cell lysates were prepared by brief sonication of harvested cells in Buffer A (150 mM NaCl, 50 mM Tris-HCl, 1 mM EDTA, 2 mM dithiothreitol, 0.025% of sodium azide, 1 mM phenylmethylsulfonyl fluoride, 1% of Triton X-100, and appropriate amounts of protease inhibitor mixture, pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, mice harboring a hypomorphic allele of LPCAT1 succumb to perinatal death from reduced surfactant (6). LPCAT1 tightly maintains surfactant balance in cells by regulating de novo synthesis of PtdCho (7). The data thus far underscore the potentially critical role of this enzyme biologically, and yet limited data are available on its molecular control.…”

Section: Phosphatidylcholine (Ptdcho)mentioning

confidence: 99%

LPS Impairs Phospholipid Synthesis by Triggering β-Transducin Repeat-containing Protein (β-TrCP)-mediated Polyubiquitination and Degradation of the Surfactant Enzyme Acyl-CoA:Lysophosphatidylcholine Acyltransferase I (LPCAT1)

Zou

Butler

Coon

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

with Arg abrogated LPCAT1 polyubiquitination. LPS profoundly reduced immunoreactive LPCAT1 levels and impaired lung surfactant mechanics, effects that were overcome by siRNA to ␤-TrCP and GSK-3␤ or LPCAT1 gene transfer, respectively. Thus, LPS appears to destabilize the LPCAT1 protein by GSK-3␤-mediated phosphorylation within a canonical phosphodegron for ␤-TrCP docking and site-specific ubiquitination. LPCAT1 is the first lipogenic substrate for ␤-TrCP, and the results suggest that modulation of the GSK-3␤-SCF␤ TrCP E3 ligase effector pathway might be a unique strategy to optimize dipalmitoylphosphatidylcholine levels in sepsis.

show abstract

“…44 All mutant constructs were generated using PCR-based approaches using appropriate primers or site-directed mutagenesis as described previously. 28 …”

Section: Quantitative Rt-pcr Cloning and Mutagenesismentioning

confidence: 99%

F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation

Chen

Glasser

Coon

et al. 2012

Blood

Self Cite

View full text Add to dashboard Cite

AbstractHematologic maligancies exhibit a growth advantage by up-regulation of components within the molecular apparatus involved in cell-cycle progression. The SCF (Skip-Cullin1-F-box protein) E3 ligase family provides homeostatic feedback control of cell division by mediating ubiquitination and degradation of cell-cycle proteins. By screening several previously undescribed E3 ligase components, we describe the behavior of a relatively new SCF subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G0 phase arrest and apoptosis in leukemic and B-lymphoblastoid cell lines. FBXL2 expression was strongly suppressed, and yet cyclin D2 protein levels were robustly expressed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patient samples. Depletion of endogenous FBXL2 stabilized cyclin D2 levels, whereas ectopically expressed FBXL2 decreased cyclin D2 lifespan. FBXL2 did not bind a phosphodegron within its substrate, which is typical of other F-box proteins, but uniquely targeted a calmodulin-binding signature within cyclin D2 to facilitate its polyubiquitination. Calmodulin competes with the F-box protein for access to this motif where it bound and protected cyclin D2 from FBXL2. Calmodulin reversed FBXL2-induced G0 phase arrest and attenuated FBXL2-induced apoptosis of lymphoblastoid cells. These results suggest an antiproliferative effect of SCFFBXL2 in lymphoproliferative malignancies.

show abstract

Cross-talk between Remodeling and de Novo Pathways Maintains Phospholipid Balance through Ubiquitination

Cited by 35 publications

References 57 publications

Cold Temperature Induces the Reprogramming of Proteolytic Pathways in Yeast

Cold Temperature Induces the Reprogramming of Proteolytic Pathways in Yeast

LPS Impairs Phospholipid Synthesis by Triggering β-Transducin Repeat-containing Protein (β-TrCP)-mediated Polyubiquitination and Degradation of the Surfactant Enzyme Acyl-CoA:Lysophosphatidylcholine Acyltransferase I (LPCAT1)

F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation

Contact Info

Product

Resources

About