更新于：2024-11-01

HTRA2

更新于：2024-11-01

基本信息

别名

High temperature requirement protein A2、HtrA serine peptidase 2、HTRA2

+ [7]

简介

Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.

关联

项与 HTRA2 相关的药物

Ahp-10

靶点

HTRA1 x HTRA2

作用机制

HTRA1抑制剂 [+1]

在研机构

University of Duisburg-Essen [+1]

原研机构

University of Duisburg-Essen

在研适应症

黄斑变性 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HTRA2 相关的临床结果

登录后查看更多信息

100 项与 HTRA2 相关的转化医学

登录后查看更多信息

0 项与 HTRA2 相关的专利（医药）

登录后查看更多信息

661

项与 HTRA2 相关的文献（医药）

2024-08-01·Ageing Research Reviews

Intracellular effects of lithium in aging neurons

Review

作者: Inestrosa, Nibaldo C ; Godoy, Juan A ; Mira, Rodrigo G

Lithium therapy received approval during the 1970s, and it has been used for its antidepressant, antimanic, and anti-suicidal effects for acute and long-term prophylaxis and treatment of bipolar disorder (BPD). These properties have been well established; however, the molecular and cellular mechanisms remain controversial. In the past few years, many studies demonstrated that at the cellular level, lithium acts as a regulator of neurogenesis, aging, and Ca²⁺ homeostasis. At the molecular level, lithium modulates aging by inhibiting glycogen synthase kinase-3β (GSK-3β), and the phosphatidylinositol (PI) cycle; latter, lithium specifically inhibits inositol production, acting as a non-competitive inhibitor of inositol monophosphatase (IMPase). Mitochondria and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) have been related to lithium activity, and its regulation is mediated by GSK-3β degradation and inhibition. Lithium also impacts Ca²⁺ homeostasis in the mitochondria modulating the function of the lithium-permeable mitochondrial Na⁺-Ca²⁺exchanger (NCLX), affecting Ca²⁺ efflux from the mitochondrial matrix to the endoplasmic reticulum (ER). A close relationship between the protease Omi, GSK-3β, and PGC-1α has also been established. The purpose of this review is to summarize some of the intracellular mechanisms related to lithium activity and how, through them, neuronal aging could be controlled.

2024-07-01·Biochemistry and Biophysics Reports

cFLIP – An interacting partner and a novel substrate for pro-apoptotic serine protease HtrA2

Article

作者: Dutta, Shubhankar ; Bose, Kakoli ; Natu, Kalyani

BackgroundHtrA2, a pro-apoptotic protease, plays a crucial role in apoptosis by cleaving inhibitory and anti-apoptotic proteins by translocating from mitochondria to the cytosol. Prior studies in ischemic cells have indicated that cytosolic HtrA2 triggers cFLIP degradation, plausibly through direct interaction. In this study, we have characterized the cFLIP protein, validated its interaction with HtrA2, and demonstrated that cFLIP is also a substrate of HtrA2.MethodsWe have identified the probable cleavage sites of cFLIP through gel-based assays and mass spectrometric analysis of the cleaved fragments.ResultsOur findings shed light on a key protein-protein interaction involving pro-apoptotic HtrA2, confirming cFLIP as its interacting partner and substrate.ConclusionUnderstanding the nuances of HtrA2's interaction with cFLIP (a decoy protein of the initiator procaspase-8 in the extrinsic apoptotic pathway) and deciphering the cFLIP's mode of cleavage, would provide an excellent alternative to modulate the pathway for therapeutic benefits toward diseases like ischemia and cancer.

2024-07-01·Molecular Diagnosis & Therapy

Exploring the Role of HtrA Family Genes in Cancer: A Systematic Review

Review

作者: Rosochowicz, Monika Anna ; Suchorska, Wiktoria Maria ; Kulcenty, Katarzyna

PURPOSEHtrA1, HtrA2, HtrA3 and HtrA4 appear to be involved in the development of pathologies such as cancer. This systematic review reports the results of a literature search performed to compare the expression of HtrA family genes and proteins in cancer versus non-cancer tissues and cell lines, assess relationships between HtrA expression and cancer clinical features in cancer, and analyse the molecular mechanism, by which HtrA family affects cancer.METHODSThe literature search was conducted according to the PRISMA statement among four databases (PubMed, Web of Science, Embase and Scopus).RESULTSA total of 38 articles met the inclusion criteria and involved the expression of HtrA family members and concerned the effect of HtrA expression on cancer and metastasis development or on the factor that influences it. Additionally, 31 reports were retrieved manually. Most articles highlighted that HtrA1 and HtrA3 exhibited tumour suppressor activity, while HtrA2 was associated with tumour growth and metastasis. There were too few studies to clearly define the role of the HtrA4 protease in tumours.CONCLUSIONAlthough the expression of serine proteases of the HtrA family was dependent on tumour type, stage and the presence of metastases, most articles indicated that HtrA1 and HtrA3 expression in tumours was downregulated compared with healthy tissue or cell lines. The expression of HtrA2 was completely study dependent. The limited number of studies on HtrA4 expression made it impossible to draw conclusions about differences in expression between healthy and tumour tissue. The conclusions drawn from the study suggest that HtrA1 and HtrA3 act as tumour suppressors.