The role of pro-domains in human growth factors and cytokines

Many growth factors and cytokines are produced as larger precursors, containing pro-domains, that require proteolytic processing to release the bioactive ligand. These pro-domains can be significantly larger than the mature domains and can play an active role in the regulation of the ligands. Mining the UniProt database, we identified almost one hundred human growth factors and cytokines with pro-domains. These are spread across several unrelated protein families and vary in both their size and composition. The precise role of each pro-domain varies significantly between the protein families. Typically they are critical for controlling bioactivity and protein localisation, and they facilitate diverse mechanisms of activation. Significant gaps in our understanding remain for pro-domain function — particularly their fate once the bioactive ligand has been released. Here we provide an overview of pro-domain roles in human growth factors and cytokines, their processing, regulation and activation, localisation as well as therapeutic potential.

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Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

Frontiers in Endocrinology ◽

10.3389/fendo.2020.612396 ◽

2021 ◽

Vol 11 ◽

Author(s):

Codruţa Şoica ◽

Mirela Voicu ◽

Roxana Ghiulai ◽

Cristina Dehelean ◽

Roxana Racoviceanu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Therapeutic Potential ◽

Treatment Options ◽

Active Role ◽

Structural Features ◽

Sex Hormone ◽

Ongoing Research ◽

New Treatment ◽

Highly Correlated

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

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

Life ◽

10.3390/life10110289 ◽

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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Xyloglucan homeostasis and microtubule dynamics synergistically maintain meristem geometry and robustness of phyllotaxis in Arabidopsis

10.1101/607481 ◽

2019 ◽

Cited By ~ 1

Author(s):

Feng Zhao ◽

Wenqian Chen ◽

Julien Sechet ◽

Marjolaine Martin ◽

Simone Bovio ◽

...

Keyword(s):

Cell Wall ◽

Biochemical Analysis ◽

Methylation Status ◽

Active Role ◽

Cellulose Content ◽

Wall Stiffness ◽

Micro Indentation ◽

Precise Role ◽

Wall Components

ABSTRACTThe shoot apical meristem (SAM) gives rise to all aerial organs of the plant. The cell walls are supposed to play a central role in this process, translating molecular regulation into dynamic changes of growth rates and directions, although their precise role in morphogenesis during organ formation remains not well understood. Here we investigate the role of xyloglucans (XyGs), which form a major, yet functionally poorly characterized, wall component in the SAM. Using immunolabeling, biochemical analysis, genetic approaches, micro-indentation, laser ablations and live imaging, we show that XyGs are important for meristem shape and phyllotaxis, although no difference in cell wall stiffness could be observed when XyGs are perturbed. Mutations in enzymes required for XyG synthesis also affect other cell wall components such as cellulose content and the pectin methylation status. Interestingly, we show that the control of cortical microtubules dynamics by the severing enzyme KATANIN becomes vital when XyGs are perturbed or absent. This suggests an active role of the cytoskeleton in compensating for altered wall composition.

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CD160 is essential for NK-mediated IFN-γ production

Journal of Experimental Medicine ◽

10.1084/jem.20131601 ◽

2015 ◽

Vol 212 (3) ◽

pp. 415-429 ◽

Cited By ~ 53

Author(s):

Tony C. Tu ◽

Nicholas K. Brown ◽

Tae-Jin Kim ◽

Joanna Wroblewska ◽

Xuanming Yang ◽

...

Keyword(s):

Nk Cells ◽

Cytokine Production ◽

Nk Cell ◽

Therapeutic Potential ◽

Tumor Regression ◽

Cell Subset ◽

Active Role ◽

Tumor Control ◽

Ifn Γ

NK-derived cytokines play important roles for natural killer (NK) function, but how the cytokines are regulated is poorly understood. CD160 is expressed on activated NK or T cells in humans but its function is unknown. We generated CD160-deficient mice to probe its function. Although CD160−/− mice showed no abnormalities in lymphocyte development, the control of NK-sensitive tumors was severely compromised in CD160−/− mice. Surprisingly, the cytotoxicity of NK cells was not impaired, but interferon-γ (IFN-γ) secretion by NK cells was markedly reduced in CD160−/− mice. Functionally targeting CD160 signaling with a soluble CD160-Ig also impaired tumor control and IFN-γ production, suggesting an active role of CD160 signaling. Using reciprocal bone marrow transfer and cell culture, we have identified the intrinsic role of CD160 on NK cells, as well as its receptor on non-NK cells, for regulating cytokine production. To demonstrate sufficiency of the CD160+ NK cell subset in controlling NK-dependent tumor growth, intratumoral transfer of the CD160+ NK fraction led to tumor regression in CD160−/− tumor-bearing mice, indicating demonstrable therapeutic potential for controlling early tumors. Therefore, CD160 is not only an important biomarker but also functionally controls cytokine production by NK cells.

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In vivoEffects of the Insulin-Like Growth Factors (IGFs) in the Hypophysectomized Rat: Comparison with Human Growth Hormone and the Possible Role of the Specific IGF Carrier Proteins

Novartis Foundation Symposia - Ciba Foundation Symposium 116 - Growth Factors in Biology and Medicine ◽

10.1002/9780470720974.ch11 ◽

2008 ◽

pp. 169-187 ◽

Cited By ~ 2

Author(s):

J. Zapf ◽

E. Schoenle ◽

E. R. Froesch

Keyword(s):

Growth Hormone ◽

Growth Factors ◽

Human Growth Hormone ◽

Human Growth ◽

Carrier Proteins ◽

Insulin Like Growth Factors

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Role of spectrin in membrane fusion and in shape change of human erythrocyte ghost

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100082509 ◽

1978 ◽

Vol 36 (2) ◽

pp. 328-329

Author(s):

Hideo Hayashi ◽

Yoshikazu Hirai ◽

John T. Penniston

Keyword(s):

Conformational Changes ◽

Human Erythrocyte ◽

Shape Change ◽

Membrane Surface ◽

Slight Modification ◽

Active Role ◽

Main Role ◽

Bank Blood ◽

Human Erythrocyte Ghost

Spectrin is a membrane associated protein most of which properties have been tentatively elucidated. A main role of the protein has been assumed to give a supporting structure to inside of the membrane. As reported previously, however, the isolated spectrin molecule underwent self assemble to form such as fibrous, meshwork, dispersed or aggregated arrangements depending upon the buffer suspended and was suggested to play an active role in the membrane conformational changes. In this study, the role of spectrin and actin was examined in terms of the molecular arrangements on the erythrocyte membrane surface with correlation to the functional states of the ghosts.Human erythrocyte ghosts were prepared from either freshly drawn or stocked bank blood by the method of Dodge et al with a slight modification as described before. Anti-spectrin antibody was raised against rabbit by injection of purified spectrin and partially purified.

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Elucidation of block boundaries as the dissolution channels in hydrated cement

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100109562 ◽

1978 ◽

Vol 36 (1) ◽

pp. 484-485

Author(s):

N.V. Belov ◽

U.I. Papiashwili ◽

B.E. Yudovich

Keyword(s):

Liquid Phase ◽

Grain Boundaries ◽

Benzoyl Peroxide ◽

Phase Contrast ◽

Active Role ◽

Point Of View ◽

Hardened Cement ◽

Hydrated Cement ◽

Hardened Cement Paste

It has been almost universally adopted that dissolution of solids proceeds with development of uniform, continuous frontiers of reaction.However this point of view is doubtful / 1 /. E.g. we have proved the active role of the block (grain) boundaries in the main phases of cement, these boundaries being the areas of hydrate phases' nucleation / 2 /. It has brought to the supposition that the dissolution frontier of cement particles in water is discrete. It seems also probable that the dissolution proceeds through the channels, which serve both for the liquid phase movement and for the drainage of the incongruant solution products. These channels can be appeared along the block boundaries.In order to demonsrate it, we have offered the method of phase-contrast impregnation of the hardened cement paste with the solution of methyl metacrylahe and benzoyl peroxide. The viscosity of this solution is equal to that of water.

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