scholarly journals Chaperonin 60: a paradoxical, evolutionarily conserved protein family with multiple moonlighting functions

2013 ◽  
Vol 88 (4) ◽  
pp. 955-987 ◽  
Author(s):  
Brian Henderson ◽  
Mario A. Fares ◽  
Peter A. Lund
Keyword(s):  
Protein Family ◽  
Evolutionarily Conserved ◽  
Chaperonin 60 ◽  
Moonlighting Functions

scholarly journals Tribbles in normal and malignant haematopoiesis

2015 ◽  
Vol 43 (5) ◽  
pp. 1112-1115 ◽  
Author(s):  
Sarah J. Stein ◽  
Ethan A. Mack ◽  
Kelly S. Rome ◽  
Warren S. Pear
Keyword(s):  
E3 Ligase ◽  
Cell Types ◽  
Protein Family ◽  
Conserved Motifs ◽  
Tissue Specific ◽  
Cellular Events ◽  
Haematopoietic Cells ◽  
Evolutionarily Conserved ◽  
Multiple Cell

The tribbles protein family, an evolutionarily conserved group of pseudokinases, have been shown to regulate multiple cellular events including those involved in normal and malignant haematopoiesis. The three mammalian Tribbles homologues, Trib1, Trib2 and Trib3 are characterized by conserved motifs, including a pseudokinase domain and a C-terminal E3 ligase-binding domain. In this review, we focus on the role of Trib (mammalian Tribbles homologues) proteins in mammalian haematopoiesis and leukaemia. The Trib proteins show divergent expression in haematopoietic cells, probably indicating cell-specific functions. The roles of the Trib proteins in oncogenesis are also varied and appear to be tissue-specific. Finally, we discuss the potential mechanisms by which the Trib proteins preferentially regulate these processes in multiple cell types.

scholarly journals A Novel Cas Family Member, HEPL, Regulates FAK and Cell Spreading

2008 ◽  
Vol 19 (4) ◽  
pp. 1627-1636 ◽  
Author(s):  
Mahendra K. Singh ◽  
Disha Dadke ◽  
Emmanuelle Nicolas ◽  
Ilya G. Serebriiskii ◽  
Sinoula Apostolou ◽  
...  
Keyword(s):  
Family Member ◽  
Cell Invasion ◽  
Focal Adhesions ◽  
Cell Spreading ◽  
Protein Family ◽  
Scaffolding Protein ◽  
Family Function ◽  
Evolutionarily Conserved ◽  
Complete Protein ◽  
Cas Proteins

For over a decade, p130Cas/BCAR1, HEF1/NEDD9/Cas-L, and Efs/Sin have defined the Cas (Crk-associated substrate) scaffolding protein family. Cas proteins mediate integrin-dependent signals at focal adhesions, regulating cell invasion and survival; at least one family member, HEF1, regulates mitosis. We here report a previously undescribed novel branch of the Cas protein family, designated HEPL (for HEF1-Efs-p130Cas-like). The HEPL branch is evolutionarily conserved through jawed vertebrates, and HEPL is found in some species lacking other members of the Cas family. The human HEPL mRNA and protein are selectively expressed in specific primary tissues and cancer cell lines, and HEPL maintains Cas family function in localization to focal adhesions, as well as regulation of FAK activity, focal adhesion integrity, and cell spreading. It has recently been demonstrated that upregulation of HEF1 expression marks and induces metastasis, whereas high endogenous levels of p130Cas are associated with poor prognosis in breast cancer, emphasizing the clinical relevance of Cas proteins. Better understanding of the complete protein family should help inform prediction of cancer incidence and prognosis.

scholarly journals The Evolutionary Conserved Transmembrane BAX Inhibitor Motif (TMBIM) Containing Protein Family is Essential for the Development and Survival of Drosophila Melanogaster

2020 ◽  
Author(s):  
Li Zhang ◽  
Sebastian Buhr ◽  
Vibha Prasad ◽  
Aaron Voigt ◽  
Axel Methner
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Interaction ◽  
Family Members ◽  
Protein Family ◽  
Tissue Specific ◽  
Similar Expression Pattern ◽  
Evolutionarily Conserved ◽  
Extended Lifespan ◽  
Ph Dependent ◽  
Er Calcium

Abstract The Transmembrane BAX Inhibitor Motif (TMBIM) protein family consists of six evolutionarily conserved hydrophobic proteins that affect programmed cell death and the regulation of intracellular calcium levels. The bacterial orthologue BsYetJ is a pH-dependent calcium channel. We here identified six TMBIM family members in Drosophila melanogaster and studied the effect of their RNAi-mediated knockdown using ubiquitous and tissue-specific drivers. Mammalian TMBIM6 and TMBIM5 have obvious orthologs while this is more dubious for the other family members. Ubiquitous knockdown of family members dmTMBIM1,4,5, and 6 caused failed eclosing and tissue-specific knockdown resulted in a dramatically decreased lifespan. On the contrary, knockdown of dmTMBIM3, surprisingly, extended lifespan. Only knockdown of dmTMBIM6 increased the ER calcium levels of Pdf neurons. Neural knockdown of dmTMBIM2,3, and 4 increased ER stress, as indicated by increased Xbp1 splicing. Interestingly, TMBIM1 and TMBIM6 have a very similar expression pattern and their knockdown phenocopied each other. Also, knockdown of TMBIM1 resulted in upregulation of TMBIM6 and vice versa further suggesting a genetic interaction between these two genes. Our data demonstrate that most TMBIM proteins are essential for fly development and survival but, despite their shared protein structure, affect cell survival through different mechanisms.

BH3-only proteins — evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death

2002 ◽  
Vol 115 (8) ◽  
pp. 1567-1574 ◽  
Author(s):  
Philippe Bouillet ◽  
Andreas Strasser
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Family Members ◽  
Protein Family ◽  
Cell Stress ◽  
Protective Function ◽  
Evolutionarily Conserved ◽  
Apoptotic Cascade

The BH3-only members of the Bcl-2 protein family are essential initiators of programmed cell death and are required for apoptosis induced by cytotoxic stimuli. These proteins have evolved to recognise distinct forms of cell stress. In response, they unleash the apoptotic cascade by inactivating the protective function of the pro-survival members of the Bcl-2 family and by activating the Bax/Bax-like pro-apoptotic family members.

scholarly journals Plastin Family of Actin-Bundling Proteins: Its Functions in Leukocytes, Neurons, Intestines, and Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hiroto Shinomiya
Keyword(s):  
Vital Role ◽  
Protein Family ◽  
Actin Binding ◽  
Animal Cells ◽  
Cell Lineages ◽  
Binding Domains ◽  
Evolutionarily Conserved ◽  
Ef Hand ◽  
Solid Tissues ◽  
The Brain

Sophisticated regulation of the actin cytoskeleton by a variety of actin-binding proteins is essential for eukaryotic cells to perform their diverse functions. The plastin (also know, as fimbrin) protein family belongs to actin-bundling proteins, and the protein family is evolutionarily conserved and expressed in yeast, plant, and animal cells. Plastins are characterized by EF-hand Ca2+-binding domains and actin-binding domains and can cross-link actin filaments into higher-order assemblies like bundles. Three isoforms have been identified in mammals. T-plastin is expressed in cells from solid tissues, such as neurons in the brain. I-plastin expression is restricted to intestine and kidney; the isoform plays a vital role in the function of absorptive epithelia in these organs. L-plastin is expressed in hematopoietic cell lineages and in many types of cancer cells; the isoform is thus considered to be a useful biomarker for cancer.

scholarly journals The Evolutionary Conserved Transmembrane BAX Inhibitor Motif (TMBIM) Containing Protein Family Members 5 and 6 Are Essential for the Development and Survival of Drosophila melanogaster

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Zhang ◽  
Sebastian Buhr ◽  
Aaron Voigt ◽  
Axel Methner
Keyword(s):  
Drosophila Melanogaster ◽  
Mammalian Cells ◽  
Developmental Stages ◽  
Family Members ◽  
Protein Family ◽  
Expression Levels ◽  
Atp Production ◽  
Evolutionarily Conserved ◽  
Human Proteins ◽  
Er Calcium

The mammalian Transmembrane BAX Inhibitor Motif (TMBIM) protein family consists of six evolutionarily conserved hydrophobic proteins that affect programmed cell death and the regulation of intracellular calcium levels. The bacterial ortholog BsYetJ is a pH-dependent calcium channel. We here identified seven TMBIM family members in Drosophila melanogaster and describe their expression levels in diverse tissues and developmental stages. A phylogenetic analysis revealed that CG30379 represents the ortholog of human TMBIM4 although these two proteins are much less related than TMBIM5 (CG2076 and CG1287/Mics1) and TMBIM6 (CG7188/Bi-1) to their respective orthologs. For TMBIM1-3 the assignment is more dubious because the fly and the human proteins cluster together. We conducted a functional analysis based on expression levels and the availability of RNAi lines. This revealed that the ubiquitous knockdown of CG3798/Nmda1 and CG3814/Lfg had no effect on development while knockdown of CG2076/dTmbim5 resulted in death at the pupa stage and knockdown of CG7188/dTmbim6 in death at the embryonic stage. Ubiquitous knockdown of the second TMBIM5 paralog CG1287/Mics1 ensued in male sterility. Knockdown of dTmbim5 and 6 in muscle and neural tissue also greatly reduced lifespan through different mechanisms. Knockdown of the mitochondrial family member dTmbim5 resulted in reduced ATP production and a pro-apoptotic expression profile while knockdown of the ER protein dTmbim6 increased the ER calcium levels similar to findings in mammalian cells. Our data demonstrate that dTmbim5 and 6 are essential for fly development and survival but affect cell survival through different mechanisms.

Systems biology approach reveals possible evolutionarily conserved moonlighting functions for enolase

2015 ◽  
Vol 58 ◽  
pp. 1-8 ◽  
Author(s):  
Gabriela Prado Paludo ◽  
Karina Rodrigues Lorenzatto ◽  
Diego Bonatto ◽  
Henrique Bunselmeyer Ferreira
Keyword(s):  
Systems Biology ◽  
Evolutionarily Conserved ◽  
Moonlighting Functions
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