Proteolytic processing of laminin and the role of cryptides in tumoral biology

2022 ◽  
pp. 113-130
Author(s):  
Adriane Sousa de Siqueira ◽  
Vanessa Morais Freitas ◽  
Ruy Gastaldoni Jaeger
Keyword(s):  
Proteolytic Processing

scholarly journals Proteolytic maturation of α2δ represents a checkpoint for activation and neuronal trafficking of latent calcium channels

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Ivan Kadurin ◽  
Laurent Ferron ◽  
Simon W Rothwell ◽  
James O Meyer ◽  
Leon R Douglas ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Proteolytic Cleavage ◽  
Proteolytic Processing ◽  
Calcium Currents ◽  
Cleavage Sites ◽  
Voltage Dependent ◽  
Neuronal Processes ◽  
Associated Proteins ◽  
Synaptic Boutons

The auxiliary α2δ subunits of voltage-gated calcium channels are extracellular membrane-associated proteins, which are post-translationally cleaved into disulfide-linked polypeptides α2 and δ. We now show, using α2δ constructs containing artificial cleavage sites, that this processing is an essential step permitting voltage-dependent activation of plasma membrane N-type (CaV2.2) calcium channels. Indeed, uncleaved α2δ inhibits native calcium currents in mammalian neurons. By inducing acute cell-surface proteolytic cleavage of α2δ, voltage-dependent activation of channels is promoted, independent from the trafficking role of α2δ. Uncleaved α2δ does not support trafficking of CaV2.2 channel complexes into neuronal processes, and inhibits Ca2+ entry into synaptic boutons, and we can reverse this by controlled intracellular proteolytic cleavage. We propose a model whereby uncleaved α2δ subunits maintain immature calcium channels in an inhibited state. Proteolytic processing of α2δ then permits voltage-dependent activation of the channels, acting as a checkpoint allowing trafficking only of mature calcium channel complexes into neuronal processes.

scholarly journals PAPP-A and the IGF system in atherosclerosis: what’s up, what’s down?

2019 ◽  
Vol 317 (5) ◽  
pp. H1039-H1049 ◽  
Author(s):  
Lasse B. Steffensen ◽  
Cheryl A. Conover ◽  
Claus Oxvig
Keyword(s):  
Mouse Models ◽  
Protein A ◽  
Proteolytic Processing ◽  
Igf System ◽  
Mechanistic Insight ◽  
Igf Binding ◽  
Experimental Approaches ◽  
Igf Binding Protein ◽  
Established Role

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor-1 (IGF-1) from IGF-binding protein-2, -4, and -5 by proteolytic processing of these. The IGF system has repeatedly been suggested to be involved in the pathology of atherosclerosis, and both PAPP-A and IGF-1 are proposed biomarkers and therapeutic targets for this disease. Several experimental approaches based on atherosclerosis mouse models have been undertaken to obtain causative and mechanistic insight to the role of these molecules in atherogenesis. However, reports seem conflicting. The literature suggests that PAPP-A is detrimental, while IGF-1 is beneficial. This raises important questions that need to be addressed. Here we summarize the various studies and discuss potential underlying explanations for this seemingly inconsistency with the objective of better understanding complexities and limitations when manipulating the IGF system in mouse models of atherosclerosis. A debate clarifying what’s up and what’s down is highly warranted going forward with the ultimate goal of improving atherosclerosis therapy by targeting the IGF system.

scholarly journals Syk and Hrs Regulate TLR3-Mediated Antiviral Response in Murine Astrocytes

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Matylda B. Mielcarska ◽  
Magdalena Bossowska-Nowicka ◽  
Karolina P. Gregorczyk-Zboroch ◽  
Zbigniew Wyżewski ◽  
Lidia Szulc-Dąbrowska ◽  
...  
Keyword(s):  
Immune Responses ◽  
Signaling Pathway ◽  
Critical Role ◽  
Antiviral Response ◽  
Proteolytic Processing ◽  
Viral Dsrna ◽  
Kinase Substrate ◽  
Tlr3 Signaling ◽  
The Brain

Toll-like receptors (TLRs) sense the presence of pathogen-associated molecular patterns. Nevertheless, the mechanisms modulating TLR-triggered innate immune responses are not yet fully understood. Complex regulatory systems exist to appropriately direct immune responses against foreign or self-nucleic acids, and a critical role of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), endosomal sorting complex required for transportation-0 (ESCRT-0) subunit, has recently been implicated in the endolysosomal transportation of TLR7 and TLR9. We investigated the involvement of Syk, Hrs, and STAM in the regulation of the TLR3 signaling pathway in a murine astrocyte cell line C8-D1A following cell stimulation with a viral dsRNA mimetic. Our data uncover a relationship between TLR3 and ESCRT-0, point out Syk as dsRNA-activated kinase, and suggest the role for Syk in mediating TLR3 signaling in murine astrocytes. We show molecular events that occur shortly after dsRNA stimulation of astrocytes and result in Syk Tyr-342 phosphorylation. Further, TLR3 undergoes proteolytic processing; the resulting TLR3 N-terminal form interacts with Hrs. The knockdown of Syk and Hrs enhances TLR3-mediated antiviral response in the form of IFN-β, IL-6, and CXCL8 secretion. Understanding the role of Syk and Hrs in TLR3 immune responses is of high importance since activation and precise execution of the TLR3 signaling pathway in the brain seem to be particularly significant in mounting an effective antiviral defense. Infection of the brain with herpes simplex type 1 virus may increase the secretion of amyloid-β by neurons and astrocytes and be a causal factor in degenerative diseases such as Alzheimer’s disease. Errors in TLR3 signaling, especially related to the precise regulation of the receptor transportation and degradation, need careful observation as they may disclose foundations to identify novel or sustain known therapeutic targets.

scholarly journals Post-Translational Modification-Dependent Activity of Matrix Metalloproteinases

2019 ◽  
Vol 20 (12) ◽  
pp. 3077 ◽  
Author(s):  
Elizabeta Madzharova ◽  
Philipp Kastl ◽  
Fabio Sabino ◽  
Ulrich auf dem Keller
Keyword(s):  
Matrix Metalloproteinases ◽  
Transcriptional Control ◽  
Proteolytic Processing ◽  
Post Translational Modification ◽  
Proteolytic Activation ◽  
Control Of Gene Expression ◽  
Post Translational Modifications ◽  
Binding Partners ◽  
Secreted Proteases

Due to their capacity to process different proteins of the extracellular matrix (ECM), matrix metalloproteinases (MMPs) were initially described as a family of secreted proteases, functioning as main ECM regulators. However, through proteolytic processing of various biomolecules, MMPs also modulate intra- and extracellular pathways and networks. Thereby, they are functionally implicated in the regulation of multiple physiological and pathological processes. Consequently, MMP activity is tightly regulated through a combination of epigenetic, transcriptional, and post-transcriptional control of gene expression, proteolytic activation, post-translational modifications (PTMs), and extracellular inhibition. In addition, MMPs, their substrates and ECM binding partners are frequently modified by PTMs, which suggests an important role of PTMs in modulating the pleiotropic activities of these proteases. This review summarizes the recent progress towards understanding the role of PTMs (glycosylation, phosphorylation, glycosaminoglycans) on the activity of several members of the MMP family.

scholarly journals Expression of the Potyvirus Genome: The Role of Proteolytic Processing

1990 ◽  
pp. 124-139 ◽  
Author(s):  
William G. Dougherty ◽  
T. Dawn Parks ◽  
Holly A. Smith ◽  
John A. Lindbo
Keyword(s):  
Proteolytic Processing

scholarly journals Functional Role of Proteolytic Processing of Recombinant Myocilin in Self-Aggregation

2010 ◽  
Vol 51 (1) ◽  
pp. 72 ◽  
Author(s):  
José-Daniel Aroca-Aguilar ◽  
Francisco Martínez-Redondo ◽  
Francisco Sánchez-Sánchez ◽  
Miguel Coca-Prados ◽  
Julio Escribano
Keyword(s):  
Functional Role ◽  
Proteolytic Processing ◽  
Self Aggregation

scholarly journals Keeping α-Synuclein at Bay: A More Active Role of Molecular Chaperones in Preventing Mitochondrial Interactions and Transition to Pathological States?

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 289
Author(s):  
Emelie E. Aspholm ◽  
Irena Matečko-Burmann ◽  
Björn M. Burmann
Keyword(s):  
Molecular Chaperones ◽  
Mitochondrial Membrane ◽  
Structural Transition ◽  
Current Knowledge ◽  
Lewy Bodies ◽  
Protein Aggregates ◽  
Active Role ◽  
Proteolytic Processing ◽  
Membrane Disruption

The property of molecular chaperones to dissolve protein aggregates of Parkinson-related α-synuclein has been known for some time. Recent findings point to an even more active role of molecular chaperones preventing the transformation of α-synuclein into pathological states subsequently leading to the formation of Lewy bodies, intracellular inclusions containing protein aggregates as well as broken organelles found in the brains of Parkinson’s patients. In parallel, a short motif around Tyr39 was identified as being crucial for the aggregation of α-synuclein. Interestingly, this region is also one of the main segments in contact with a diverse pool of molecular chaperones. Further, it could be shown that the inhibition of the chaperone:α-synuclein interaction leads to a binding of α-synuclein to mitochondria, which could also be shown to lead to mitochondrial membrane disruption as well as the possible proteolytic processing of α-synuclein by mitochondrial proteases. Here, we will review the current knowledge on the role of molecular chaperones in the regulation of physiological functions as well as the direct consequences of impairing these interactions—i.e., leading to enhanced mitochondrial interaction and consequential mitochondrial breakage, which might mark the initial stages of the structural transition of α-synuclein towards its pathological states.

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