scholarly journals Prediction of Sub-cellular Localization of Scramblase Protein Family

2010 ◽  
pp. 187-195
Author(s):  
Babita Sahoo ◽  
Santosh Kumar Sahu ◽  
Tripti Swarnkar
Keyword(s):  
Subcellular Localization ◽  
Cellular Localization ◽  
Protein Family ◽  
Cellular Functions

In the present work, we discuss an anaysis about the localization of different members of scramblase protein family. Different scramblase sequences were picked up from organisms of all eukaryotic phyla and their localization were predicted using the P-SORT programme. Our analysis showed that the scramblase protein family shows multiple subcellular localization. Most proteins were found to be localized to the cytoplasm, where as others were found to be present in the nucleus or mitochondria. Interestingly, we found that in yeast, all putative scramblases were localized in the nucleus with a reliability of more than 95%. Our analysis shows that scramblases are a family of protein having diversed cellular localization and hence hypothesized to be performing multiple cellular functions in various organisms.

Investigating the functional link between TMEM165 and SPCA1

2019 ◽  
Vol 476 (21) ◽  
pp. 3281-3293 ◽  
Author(s):  
Elodie Lebredonchel ◽  
Marine Houdou ◽  
Hans-Heinrich Hoffmann ◽  
Kateryna Kondratska ◽  
Marie-Ange Krzewinski ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Complete Loss ◽  
Protein Family ◽  
Uncharacterized Protein ◽  
Functional Link ◽  
P Type

TMEM165 was highlighted in 2012 as the first member of the Uncharacterized Protein Family 0016 (UPF0016) related to human glycosylation diseases. Defects in TMEM165 are associated with strong Golgi glycosylation abnormalities. Our previous work has shown that TMEM165 rapidly degrades with supraphysiological manganese supplementation. In this paper, we establish a functional link between TMEM165 and SPCA1, the Golgi Ca2+/Mn2+ P-type ATPase pump. A nearly complete loss of TMEM165 was observed in SPCA1-deficient Hap1 cells. We demonstrate that TMEM165 was constitutively degraded in lysosomes in the absence of SPCA1. Complementation studies showed that TMEM165 abundance was directly dependent on SPCA1's function and more specifically its capacity to pump Mn2+ from the cytosol into the Golgi lumen. Among SPCA1 mutants that differentially impair Mn2+ and Ca2+ transport, only the Q747A mutant that favors Mn2+ pumping rescues the abundance and Golgi subcellular localization of TMEM165. Interestingly, the overexpression of SERCA2b also rescues the expression of TMEM165. Finally, this paper highlights that TMEM165 expression is linked to the function of SPCA1.

TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix

1994 ◽  
Vol 107 (10) ◽  
pp. 2851-2859
Author(s):  
E.C. Joly ◽  
E. Tremblay ◽  
R.M. Tanguay ◽  
Y. Wu ◽  
V. Bibor-Hardy
Keyword(s):  
Nuclear Matrix ◽  
Cellular Localization ◽  
Cell Fractionation ◽  
Cellular Functions ◽  
Raji Cells ◽  
T Complex ◽  
Ring Complex ◽  
Filament Network ◽  
Novel Protein

We have recently reported the cloning of a novel protein, TRiC-P5, with significant homology with protein 1 of the t-complex (TCP1). In the present study, the cellular localization of TRiC-P5 in Raji cells has been determined using an antiserum raised against a 18.5 kDa fusion protein. Results from cell fractionation and immunoblot studies indicate that TRiC-P5 is mainly localized in the cytoplasm. In addition, a significant part of TRiC-P5 is also found in the nucleus where it is attached to the nuclear matrix, a complex filament network involved in essential cellular functions such as DNA replication, and RNA transcription and maturation. Immunofluorescence experiments using the anti-TRiC-P5 antibodies confirm these results. We also provide evidence that, in the cytoplasm, TRiC-P5 is part of a large protein complex, most probably the TCP1-ring complex (TRiC), a hetero-oligomeric ring complex that plays a role of molecular chaperone in the folding of actin and tubulin.

Protein kinase C-α and the regulation of diverse cell responses

2017 ◽  
Vol 8 (3-4) ◽  
pp. 143-153 ◽  
Author(s):  
Rishi Kant Singh ◽  
Sanjay Kumar ◽  
Pramod Kumar Gautam ◽  
Munendra Singh Tomar ◽  
Praveen Kumar Verma ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cellular Localization ◽  
Cellular Transformation ◽  
Cell Types ◽  
Adapter Proteins ◽  
Cellular Functions ◽  
Cell Responses ◽  
Kinase C ◽  
Cellular Compartments

AbstractProtein kinase C (PKC) comprises a family of lipid-sensitive enzymes that have been involved in a broad range of cellular functions. PKC-α is a member of classical PKC with ubiquitous expression and different cellular localization. This unique PKC isoform is activated by various signals which evoke lipid hydrolysis, after activation it interacts with various adapter proteins and is localized to specific cellular compartments where it is devised to work. The universal expression and activation by various stimuli make it a perfect player in uncountable cellular functions including differentiation, proliferation, apoptosis, cellular transformation, motility, adhesion and so on. However, these functions are not intrinsic properties of PKC-α, but depend on cell types and conditions. The activities of PKC-α are managed by the various pharmacological activators/inhibitors and antisense oligonucleotides. The aim of this review is to elaborate the structural feature, and provide an insight into the mechanism of PKC-α activation and regulation of its key biological functions in different cellular compartments to develop an effective pharmacological approach to regulate the PKC-α signal array.

scholarly journals RAC1 Takes the Lead in Solid Tumors

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 382 ◽  
Author(s):  
Pradip De ◽  
Jennifer Carlson Aske ◽  
Nandini Dey
Keyword(s):  
Drug Resistance ◽  
Embryonic Development ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Cellular Localization ◽  
Regulatory Mechanisms ◽  
Cellular Functions ◽  
Patterns Of Distribution ◽  
Background Data

Three GTPases, RAC, RHO, and Cdc42, play essential roles in coordinating many cellular functions during embryonic development, both in healthy cells and in disease conditions like cancers. We have presented patterns of distribution of the frequency of RAC1-alteration(s) in cancers as obtained from cBioPortal. With this background data, we have interrogated the various functions of RAC1 in tumors, including proliferation, metastasis-associated phenotypes, and drug-resistance with a special emphasis on solid tumors in adults. We have reviewed the activation and regulation of RAC1 functions on the basis of its sub-cellular localization in tumor cells. Our review focuses on the role of RAC1 in cancers and summarizes the regulatory mechanisms, inhibitory efficacy, and the anticancer potential of RAC1-PAK targeting agents.

Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains

2013 ◽  
Vol 394 (8) ◽  
pp. 1077-1090 ◽  
Author(s):  
Kristin Wächter ◽  
Marcel Köhn ◽  
Nadine Stöhr ◽  
Stefan Hüttelmaier
Keyword(s):  
Subcellular Localization ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Accumulation ◽  
Structural Constraints ◽  
Cellular Functions ◽  
Dependent Protein ◽  
Mrna Binding

Abstract The IGF2 mRNA-binding protein family (IGF2BPs) directs the cytoplasmic fate of various target mRNAs and controls essential cellular functions. The three IGF2BP paralogues expressed in mammals comprise two RNA-recognition motifs (RRM) as well as four KH domains. How these domains direct IGF2BP paralogue-dependent protein function remains largely elusive. In this study, we analyze the role of KH domains in IGF2BPs by the mutational GXXG-GEEG conversion of single KH domain loops in the context of full-length polypeptides. These analyses reveal that all four KH domains of IGF2BP1 and IGF2BP2 are essentially involved in RNA-binding in vitro and the cellular association with RNA-binding proteins (RBPs). Moreover the KH domains prevent the nuclear accumulation of these two paralogues and facilitate their recruitment to stress granules. The role of KH domains appears less pronounced in IGF2BP3, because GxxG-GEEG conversion in all four KH domains only modestly affects RNA-binding, subcellular localization and RNA-dependent protein association of this paralogue. These findings indicate paralogue-dependent RNA-binding properties of IGF2BPs which likely direct distinct cellular functions. Our findings suggest that IGF2BPs contact target RNAs via all four KH domains. This implies significant structural constraints, which presumably allow the formation of exceedingly stable protein-RNA complexes.

scholarly journals Subcellular localization of EEN/endophilin A2, a fusion partner gene in leukaemia

2004 ◽  
Vol 383 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Ngai CHEUNG ◽  
Chi Wai SO ◽  
Judy W. P. YAM ◽  
C. K. C. SO ◽  
Randy Y. C. POON ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Fusion Partner ◽  
Nucleocytoplasmic Shuttling ◽  
Cellular Functions ◽  
Protein Levels ◽  
Mixed Lineage Leukaemia ◽  
Partner Gene ◽  
M Phase ◽  
Endocytic Vesicles

EEN (extra eleven nineteen), also known as EA2 (endophilin A2), a fusion partner of the MLL (mixed-lineage leukaemia) gene in human acute leukaemia, is a member of the endophilin A family, involved in the formation of endocytic vesicles. We present evidence to show that EEN/EA2 is localized predominantly in nuclei of various cell lines of haemopoietic, fibroblast and epithelial origin, in contrast with its reported cytoplasmic localization in neurons and osteoclasts, and that EEN/EA2 exhibits nucleocytoplasmic shuttling. During the cell cycle, EEN/EA2 shows dynamic localization: it is perichromosomal in prometaphase, co-localizes with the bipolar spindle in metaphase and anaphase and redistributes to the midzone and midbody in telophase. This pattern of distribution coincides with changes in protein levels of EEN/EA2, with the highest levels being observed in G2/M-phase. Our results suggest that distinct subcellular localization of the endophilin A family members probably underpins their diverse cellular functions and indicates a role for EEN/EA2 in the cell cycle.

The Akt isoforms are present at distinct subcellular locations

2010 ◽  
Vol 298 (3) ◽  
pp. C580-C591 ◽  
Author(s):  
Stacey A. Santi ◽  
Hoyun Lee
Keyword(s):  
Energy Metabolism ◽  
Subcellular Localization ◽  
Subcellular Location ◽  
T Antigen ◽  
Sv40 T Antigen ◽  
Cellular Functions ◽  
Hek 293 ◽  
Major Function ◽  
Akt Isoforms ◽  
Interfering Rna

Akt is involved in the regulation of diverse cellular functions such as cell proliferation, energy metabolism, and apoptosis. Although three Akt isoforms are known, the function of each isoform is poorly understood. To gain a better understanding of each Akt isoform, we examined the subcellular localization and expression of each isoform in transformed and nontransformed cells. Akt1 was localized in the cytoplasm, which is in agreement with the currently accepted model that cytoplasmic Akt is translocated and activated at the inner leaflet of the plasma membrane. Interestingly, HEK-293 and HEK-293T cells contained Akt1 in the nucleus and cytoplasm, respectively, suggesting that SV40 T-antigen plays a crucial role in the cytoplasmic localization and activation of Akt1 in HEK-293T. Akt2 was colocalized with the mitochondria, while Akt3 was localized in both the nucleus and nuclear membrane. The subcellular localization of the Akt isoforms was not substantially altered in response to ionizing radiation or EGF. Furthermore, the ablation of one Akt isoform by small interfering RNA (siRNA) did not alter the subcellular location of the remaining isoforms, suggesting that the major function of one isoform is not compensated for by other isoforms. Together, our data support the notion that Akt2 and Akt3 are regulated at the mitochondrial and nuclear membranes, respectively. The mitochondrial localization of Akt2 raises the possibility that this isoform may be involved in both glucose-based energy metabolism and suppression of apoptosis, two Akt functions previously identified with anti-pan-Akt antibodies.

scholarly journals Members of the GADD45 Protein Family Show Distinct Propensities to form Toxic Amyloid-Like Aggregates in Physiological Conditions

2021 ◽  
Vol 22 (19) ◽  
pp. 10700
Author(s):  
Giovanni Smaldone ◽  
Daniela Caruso ◽  
Annamaria Sandomenico ◽  
Emanuela Iaccarino ◽  
Annalia Focà ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Protein Family ◽  
Label Free ◽  
Cellular Functions ◽  
Physiological Conditions ◽  
Toxic Species ◽  
High Molecular Weight Species ◽  
Functional Implications ◽  
Uv Visible ◽  
Strong Interactors

The three members (GADD45α, GADD45β, and GADD45γ) of the growth arrest and DNA damage-inducible 45 (GADD45) protein family are involved in a myriad of diversified cellular functions. With the aim of unravelling analogies and differences, we performed comparative biochemical and biophysical analyses on the three proteins. The characterization and quantification of their binding to the MKK7 kinase, a validated functional partner of GADD45β, indicate that GADD45α and GADD45γ are strong interactors of the kinase. Despite their remarkable sequence similarity, the three proteins present rather distinct biophysical properties. Indeed, while GADD45β and GADD45γ are marginally stable at physiological temperatures, GADD45α presents the Tm value expected for a protein isolated from a mesophilic organism. Surprisingly, GADD45α and GADD45β, when heated, form high-molecular weight species that exhibit features (ThT binding and intrinsic label-free UV/visible fluorescence) proper of amyloid-like aggregates. Cell viability studies demonstrate that they are endowed with a remarkable toxicity against SHSY-5Y and HepG2 cells. The very uncommon property of GADD45β to form cytotoxic species in near-physiological conditions represents a puzzling finding with potential functional implications. Finally, the low stability and/or the propensity to form toxic species of GADD45 proteins constitute important features that should be considered in interpreting their many functions.

scholarly journals Does it take two to tango? RING domain self-association and activity in TRIM E3 ubiquitin ligases

2020 ◽  
Vol 48 (6) ◽  
pp. 2615-2624
Author(s):  
Filippo Fiorentini ◽  
Diego Esposito ◽  
Katrin Rittinger
Keyword(s):  
Coiled Coil ◽  
E3 Ligase ◽  
Protein Family ◽  
Ring Domain ◽  
Cellular Functions ◽  
Protein Activity ◽  
Coiled Coil Region ◽  
Tripartite Motif ◽  
Large Protein Family ◽  
Self Association

TRIM proteins form a protein family that is characterized by a conserved tripartite motif domain comprising a RING domain, one or two B-box domains and a coiled-coil region. Members of this large protein family are important regulators of numerous cellular functions including innate immune responses, transcriptional regulation and apoptosis. Key to their cellular role is their E3 ligase activity which is conferred by the RING domain. Self-association is an important characteristic of TRIM protein activity and is mediated by homodimerization via the coiled-coil region, and in some cases higher order association via additional domains of the tripartite motif. In many of the TRIM family proteins studied thus far, RING dimerization is an important prerequisite for E3 ligase enzymatic activity though the propensity of RING domains to dimerize differs significantly between different TRIMs and can be influenced by other regions of the protein.

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