Osteopontin in Cancer: Mechanisms and Therapeutic Targets DOI Creative Commons
Yoshinobu Kariya,

Yukiko Kariya

International Journal of Translational Medicine, Год журнала: 2022, Номер 2(3), С. 419 - 447

Опубликована: Авг. 19, 2022

Despite significant advances in the understanding of cancer biology, is still a leading cause death worldwide. Expression tumor microenvironment component, osteopontin, tissues, plasma, and serum, has been shown to be associated with poor prognosis survival rate various human cancers. Recent studies suggest that osteopontin drives development aggressiveness using strategies. In this review, we first provide an overview how promotes progression, such as growth, invasion, angiogenesis, immune modulation, well metastasis chemoresistance. Next, address functional activities are modulated by interaction integrins CD44 receptors, but also post-translational modification, proteolytic processing several proteases, phosphorylation, glycosylation. Then, review activates tumor-associated macrophages (TAMs) cancer-associated fibroblasts (CAFs), functions immunosuppressor regulating surveillance checkpoint microenvironment. Finally, discuss potential applications biomarker therapeutic target.

Язык: Английский

Light-regulated allosteric switch enables temporal and subcellular control of enzyme activity DOI Creative Commons
Mark Shaaya, Jordan Fauser, Anastasia Zhurikhina

и другие.

eLife, Год журнала: 2020, Номер 9

Опубликована: Сен. 23, 2020

Engineered allosteric regulation of protein activity provides significant advantages for the development robust and broadly applicable tools. However, application switches in optogenetics has been scarce suffers from critical limitations. Here, we report an optogenetic approach that utilizes engineered Light-Regulated (LightR) switch module to achieve tight spatiotemporal control enzymatic activity. Using tyrosine kinase Src as a model, demonstrate efficient identify temporally distinct signaling responses ranging seconds minutes. LightR-Src off-kinetics can be tuned by modulating LightR photoconversion cycle. A fast cycling variant enables stimulation transient pulses local selected region cell. The design ensures broad applicability tool, achieving light-mediated Abl bRaf kinases well Cre recombinase.

Язык: Английский

Процитировано

48

MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells DOI Creative Commons
Qiaozhi Wei, Sandra Pinho, Shuxian Dong

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Май 4, 2021

Abstract Haematopoietic stem cells (HSCs) tightly regulate their quiescence, proliferation, and differentiation to generate blood during the entire lifetime. The mechanisms by which these critical activities are balanced still unclear. Here, we report that Ma crophage- E rythroblast A ttacher (MAEA, also known as EMP), a receptor thus far only identified in erythroblastic island, is membrane-associated E3 ubiquitin ligase subunit essential for HSC maintenance lymphoid potential. Maea highly expressed HSCs its deletion mice severely impairs quiescence leads lethal myeloproliferative syndrome. Mechanistically, have found surface expression of several haematopoietic cytokine receptors (e.g. MPL, FLT3) stabilised absence , thereby prolonging intracellular signalling. This associated with impaired autophagy flux but not mature cells. Administration kinase inhibitor or autophagy-inducing compounds rescues functional defects -deficient HSCs. Our results suggest MAEA provides activity, guarding function restricting signalling via autophagy.

Язык: Английский

Процитировано

37

Evolution-inspired redesign of the LPS receptor caspase-4 into an interleukin-1β–converting enzyme DOI
Pascal Devant, Anh Cao, Jonathan C. Kagan

и другие.

Science Immunology, Год журнала: 2021, Номер 6(62)

Опубликована: Авг. 6, 2021

Caspase-4 homologs can naturally evolve or be synthetically engineered to directly link cytosolic LPS detection IL-1β secretion.

Язык: Английский

Процитировано

37

The Mammalian Family of Katanin Microtubule-Severing Enzymes DOI Creative Commons

Nicole A. Lynn,

Emily Martinez,

Hieu Nguyen

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Авг. 3, 2021

The katanin family of microtubule-severing enzymes is critical for cytoskeletal rearrangements that affect key cellular processes like division, migration, signaling, and homeostasis. In humans, aberrant expression, or dysfunction the katanins, linked to developmental, proliferative, neurodegenerative disorders. Here, we review current knowledge on mammalian including an overview evolutionary conservation, functional domain organization, mechanisms regulate activity. We assess function katanins in dividing non-dividing cells how their dysregulation promotes impaired ciliary signaling defects developmental programs (corticogenesis, gametogenesis, neurodevelopment) contributes neurodegeneration cancer. conclude with perspectives future research will advance our understanding this exciting dynamic class disease-associated enzymes.

Язык: Английский

Процитировано

35

Osteopontin in Cancer: Mechanisms and Therapeutic Targets DOI Creative Commons
Yoshinobu Kariya,

Yukiko Kariya

International Journal of Translational Medicine, Год журнала: 2022, Номер 2(3), С. 419 - 447

Опубликована: Авг. 19, 2022

Despite significant advances in the understanding of cancer biology, is still a leading cause death worldwide. Expression tumor microenvironment component, osteopontin, tissues, plasma, and serum, has been shown to be associated with poor prognosis survival rate various human cancers. Recent studies suggest that osteopontin drives development aggressiveness using strategies. In this review, we first provide an overview how promotes progression, such as growth, invasion, angiogenesis, immune modulation, well metastasis chemoresistance. Next, address functional activities are modulated by interaction integrins CD44 receptors, but also post-translational modification, proteolytic processing several proteases, phosphorylation, glycosylation. Then, review activates tumor-associated macrophages (TAMs) cancer-associated fibroblasts (CAFs), functions immunosuppressor regulating surveillance checkpoint microenvironment. Finally, discuss potential applications biomarker therapeutic target.

Язык: Английский

Процитировано

27