Oligomerization Mechanisms of an H-NS Family Protein, Pmr, Encoded on the Plasmid pCAR1 Provide a Molecular Basis for Functions of H-NS Family Members

Tau is an intrinsically-disordered microtubule-associated protein (MAP) implicated in neurodegenerative disease. On microtubules, tau molecules segregate into two kinetically distinct phases, consisting of either independently diffusing molecules or interacting molecules that form cohesive envelopes around microtubules. Envelopes differentially regulate lattice accessibility for other MAPs, but the mechanism of envelope formation remains unclear. Here, we find that tau envelopes form cooperatively, locally altering the spacing of tubulin dimers within the microtubule lattice. Envelope formation compacted the underlying lattice, whereas lattice extension induced tau-envelope disassembly. Investigating other members of the tau-MAP family, we find MAP2 similarly forms envelopes governed by lattice-spacing, whereas MAP4 cannot. Envelopes differentially biased motor protein movement, suggesting that tau family members could spatially divide the microtubule surface into functionally distinct segments. We conclude that the interdependent allostery between lattice-spacing and cooperative envelope formation provides the molecular basis for spatial regulation of microtubule-based processes by tau and MAP2.

Download Full-text

Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1417620112 ◽

2015 ◽

Vol 112 (13) ◽

pp. 4044-4049 ◽

Cited By ~ 29

Author(s):

Emma M. Carrington ◽

Jian-Guo Zhang ◽

Robyn M. Sutherland ◽

Ingela B. Vikstrom ◽

Jamie L. Brady ◽

...

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Cell Survival ◽

Molecular Basis ◽

Family Members ◽

Specific Inhibitor ◽

Immune Intervention ◽

Molecular Control ◽

Plasmacytoid Dcs

Dendritic cells (DCs) are heterogeneous, comprising subsets with functional specializations that play distinct roles in immunity as well as immunopathology. We investigated the molecular control of cell survival of two main DC subsets: plasmacytoid DCs (pDCs) and conventional DCs (cDCs) and their dependence on individual antiapoptotic BCL-2 family members. Compared with cDCs, pDCs had higher expression of BCL-2, lower A1, and similar levels of MCL-1 and BCL-XL. Transgenic overexpression of BCL-2 increased the pDC pool size in vivo with only minor impact on cDCs. With a view to immune intervention, we tested BCL-2 inhibitors and found that ABT-199 (the BCL-2 specific inhibitor) selectively killed pDCs but not cDCs. Conversely, genetic knockdown of A1 profoundly reduced the proportion of cDCs but not pDCs. We also found that conditional ablation of MCL-1 significantly reduced the size of both DC populations in mice and impeded DC-mediated immune responses. Thus, we revealed that the two DC types have different cell survival requirements. The molecular basis of survival of different DC subsets thus advocates the antagonism of selective BCL-2 family members for treating diseases pertaining to distinct DC subsets.

Download Full-text

Roles of paxillin family members in adhesion and ECM degradation coupling at invadosomes

The Journal of Cell Biology ◽

10.1083/jcb.201510036 ◽

2016 ◽

Vol 213 (5) ◽

pp. 585-599 ◽

Cited By ~ 11

Author(s):

Christos Petropoulos ◽

Christiane Oddou ◽

Anouk Emadali ◽

Edwige Hiriart-Bryant ◽

Cyril Boyault ◽

...

Keyword(s):

Family Members ◽

Janus Kinase ◽

Mass Spectrometry Analysis ◽

Spectrometry Analysis ◽

Adhesion Sites ◽

Lim Domains ◽

Janus Kinase 1 ◽

Family Protein ◽

Functional Complex ◽

Ecm Degradation

Invadosomes are acto-adhesive structures able to both bind the extracellular matrix (ECM) and digest it. Paxillin family members—paxillin, Hic-5, and leupaxin—are implicated in mechanosensing and turnover of adhesion sites, but the contribution of each paxillin family protein to invadosome activities is unclear. We use genetic approaches to show that paxillin and Hic-5 have both redundant and distinctive functions in invadosome formation. The essential function of paxillin-like activity is based on the coordinated activity of LD motifs and LIM domains, which support invadosome assembly and morphology, respectively. However, paxillin preferentially regulates invadosome assembly, whereas Hic-5 regulates the coupling between ECM degradation and acto-adhesive functions. Mass spectrometry analysis revealed new partners that are important for paxillin and Hic-5 specificities: paxillin regulates the acto-adhesive machinery through janus kinase 1 (JAK1), whereas Hic-5 controls ECM degradation via IQGAP1. Integrating the redundancy and specificities of paxillin and Hic-5 in a functional complex provides insights into the coupling between the acto-adhesive and ECM-degradative machineries in invadosomes.

Download Full-text

Research Advances in the Role of the Poly ADP Ribose Polymerase Family in Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.790967 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huanhuan Sha ◽

Yujie Gan ◽

Renrui Zou ◽

Jianzhong Wu ◽

Jifeng Feng

Keyword(s):

Signaling Pathways ◽

Clinical Application ◽

Molecular Basis ◽

Rapid Development ◽

Family Members ◽

Genomic Stability ◽

Regulatory Mechanisms ◽

Breast Cancers ◽

The Future

Poly ADP ribose polymerases (PARPs) catalyze the modification of acceptor proteins, DNA, or RNA with ADP-ribose, which plays an important role in maintaining genomic stability and regulating signaling pathways. The rapid development of PARP1/2 inhibitors for the treatment of ovarian and breast cancers has advanced research on other PARP family members for the treatment of cancer. This paper reviews the role of PARP family members (except PARP1/2 and tankyrases) in cancer and the underlying regulatory mechanisms, which will establish a molecular basis for the clinical application of PARPs in the future.

Download Full-text

The prognostic values of the peroxiredoxins family in ovarian cancer

Bioscience Reports ◽

10.1042/bsr20180667 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 12

Author(s):

Saisai Li ◽

Xiaoli Hu ◽

Miaomiao Ye ◽

Xueqiong Zhu

Keyword(s):

Ovarian Cancer ◽

Protein Expression ◽

Cancer Patients ◽

Expression Profiles ◽

Family Members ◽

Progression Free Survival ◽

Prognostic Indicator ◽

Chemotherapeutic Agents ◽

Family Protein ◽

Cancer Tissues

Purpose: Peroxiredoxins (PRDXs) are a family of antioxidant enzymes with six identified mammalian isoforms (PRDX1–6). PRDX expression is up-regulated in various types of solid tumors; however, individual PRDX expression, and its impact on prognostic value in ovarian cancer patients, remains unclear.Methods: PRDXs family protein expression profiles in normal ovarian tissues and ovarian cancer tissues were examined using the Human Protein Atlas database. Then, the prognostic roles of PRDX family members in several sets of clinical data (histology, pathological grades, clinical stages, and applied chemotherapy) in ovarian cancer patients were investigated using the Kaplan–Meier plotter.Results: PRDXs family protein expression in ovarian cancer tissues was elevated compared with normal ovarian tissues. Meanwhile, elevated expression of PRDX3, PRDX5, and PRDX6 mRNAs showed poorer overall survival (OS); PRDX5 and PRDX6 also predicted poor progression-free survival (PFS) for ovarian cancer patients. Furthermore, PRDX3 played significant prognostic roles, particularly in poor differentiation and late-stage serous ovarian cancer patients. Additionally, PRDX5 predicted a lower PFS in all ovarian cancer patients treated with Platin, Taxol, and Taxol+Platin chemotherapy. PRDX3 and PRDX6 also showed poor PFS in patients treated with Platin chemotherapy. Furthermore, PRDX3 and PRDX5 indicated lower OS in patients treated with these three chemotherapeutic agents. PRDX6 predicted a poorer OS in patients treated with Taxol and Taxol+Platin chemotherapy.Conclusion: These results suggest that there are distinct prognostic values of PRDX family members in patients with ovarian cancer, and that the expression of PRDX3, PRDX5, and PRDX6 mRNAs are a useful prognostic indicator in the effect of chemotherapy in ovarian cancer patients.

Download Full-text

S1704 The Molecular Basis Responsible for High Affinity of All Human Bombesin Receptor (BnR) Family Members for a Universal Ligand (Un. Lig.)

Gastroenterology ◽

10.1016/s0016-5085(10)61174-2 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-257

Author(s):

Hirotsugu Uehara ◽

Nieves Gonzalez ◽

Samuel A. Mantey ◽

Tomoo Nakagawa ◽

Tatsuro Katsuno ◽

...

Keyword(s):

Molecular Basis ◽

Family Members ◽

High Affinity ◽

Bombesin Receptor

Download Full-text

Histone benzoylation serves as an epigenetic mark for DPF and YEATS family proteins

Nucleic Acids Research ◽

10.1093/nar/gkaa1130 ◽

2020 ◽

Author(s):

Xiangle Ren ◽

Yang Zhou ◽

Zhaoyu Xue ◽

Ning Hao ◽

Yuanyuan Li ◽

...

Keyword(s):

Molecular Basis ◽

Cultured Cells ◽

Family Members ◽

The Other ◽

Epigenetic Mark ◽

Lysine Acetylation ◽

Binding Studies ◽

Dynamic Regulation ◽

Active Transcription ◽

Crystal Structural

Abstract Histone modifications and their functional readout serve as an important mechanism for gene regulation. Lysine benzoylation (Kbz) on histones is a recently identified acylation mark associated with active transcription. However, it remains to be explored whether putative readers exist to recognize this epigenetic mark. Here, our systematic binding studies demonstrated that the DPF and YEATS, but not the Bromodomain family members, are readers for histone Kbz. Co-crystal structural analyses revealed a ‘hydrophobic encapsulation’ and a ‘tip-sensor’ mechanism for Kbz readout by DPF and YEATS, respectively. Moreover, the DPF and YEATS family members display subtle yet unique features to create somewhat flexible engagements of different acylation marks. For instance, YEATS2 but not the other YEATS proteins exhibits best preference for Kbz than lysine acetylation and crotonylation due to its wider ‘tip-sensor’ pocket. The levels of histone benzoylation in cultured cells or in mice are upregulated upon sodium benzoate treatment, highlighting its dynamic regulation. In summary, our work identifies the first readers for histone Kbz and reveals the molecular basis underlying Kbz recognition, thus paving the way for further functional dissections of histone benzoylation.

Download Full-text

Renilla Bioluminescence: A Morphologic Approach to the Location of Photocytes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051050 ◽

1974 ◽

Vol 32 ◽

pp. 208-209

Author(s):

Ben O. Spurlock ◽

Milton J. Cormier

Keyword(s):

Excited State ◽

Ground State ◽

Molecular Basis ◽

Light Emission ◽

Chemical Basis ◽

Electronic Excited State ◽

Colonial Form ◽

The Common ◽

Eighteenth And Nineteenth Centuries ◽

Catalyzed Oxidation

The phenomenon of bioluminescence has fascinated layman and scientist alike for many centuries. During the eighteenth and nineteenth centuries a number of observations were reported on the physiology of bioluminescence in Renilla, the common sea pansy. More recently biochemists have directed their attention to the molecular basis of luminosity in this colonial form. These studies have centered primarily on defining the chemical basis for bioluminescence and its control. It is now established that bioluminescence in Renilla arises due to the luciferase-catalyzed oxidation of luciferin. This results in the creation of a product (oxyluciferin) in an electronic excited state. The transition of oxyluciferin from its excited state to the ground state leads to light emission.

Download Full-text

Androgen-induced plasticity at a “vocal” neuromuscular synapse

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100167895 ◽

1994 ◽

Vol 52 ◽

pp. 32-33

Author(s):

Darcy B. Kelley ◽

Martha L. Tobias ◽

Mark Ellisman

Keyword(s):

Xenopus Laevis ◽

Motor Neurons ◽

Sexual Differentiation ◽

Molecular Basis ◽

Neuromuscular Synapse ◽

Sexually Dimorphic ◽

Intracellular Protein ◽

Developmental Program ◽

Androgen Action ◽

Clawed Frog

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.

Download Full-text