J 2008

CATHEPSIN D : MANY FUNCTIONS OF ONE ASPARTIC PROTEASE

BENEŠ, Petr, Václav VĚTVIČKA and Martin FUSEK

Basic information

Original name

CATHEPSIN D : MANY FUNCTIONS OF ONE ASPARTIC PROTEASE

Name in Czech

Katepsin D : mnoho funkcí jediné aspartátové proteázy

Authors

BENEŠ, Petr (203 Czech Republic, guarantor), Václav VĚTVIČKA (203 Czech Republic) and Martin FUSEK (203 Czech Republic)

Edition

Critical Reviews in Oncology/Hematology, ELSEVIER, 2008, 1040-8428

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 4.589

RIV identification code

RIV/00216224:14310/08:00024162

Organization unit

Faculty of Science

UT WoS

000259895900002

Keywords in English

Alzheimer disease; Apoptosis; Atherosclerosis; Aspartic protease; Cancer; Cathepsin D; Knock-out mice; Procathepsin D

Tags

International impact, Reviewed
Změněno: 25/6/2009 12:19, doc. Mgr. Petr Beneš, Ph.D.

Abstract

V originále

For years, it has been held that cathepsin D (CD) is involved in rather non-specific protein degradation in a strongly acidic milieu of lysosomes. Studies with CD knock-out mice revealed that CD is not necessary for embryonal development, but it is indispensable for postnatal tissue homeostasis. Mutation that abolishes CD enzymatic activity causes neuronal ceroid lipofuscinosis (NCL) characterized by severe neurodegeneration, developmental regression, visual loss and epilepsy in both animals and humans. In the last decade, however, an increasing number of studies demonstrated that enzymatic function of CD is not restricted solely to acidic milieu of lysosomes with important consequences in regulation of apoptosis. In addition to CD enzymatic activity, it has been shown that apoptosis is also regulated by catalytically inactive mutants of CD which suggests that CD interacts with other important molecules and influences cell signaling. Moreover, procathepsin D (pCD), secreted from cancer cells, acts as a mitogen on both cancer and stromal cells and stimulates their pro-invasive and pro-metastatic properties. Numerous studies found that pCD/CD level represents an independent prognostic factor in a variety of cancers and is therefore considered to be a potential target of anti-cancer therapy. Studies dealing with functions of cathepsin D are complicated by the fact that there are several simultaneous forms of CD in a cell-pCD, intermediate enzymatically active CD and mature heavy and light chain CD. It became evident that these forms may differently regulate the above-mentioned processes. In this article, we review the possible functions of CD and its various forms in cells and organisms during physiological and pathological conditions.

In Czech

Tento přehledný článek shrnuje nejnovější poznatky o úloze různých forem katepsinu D ve fyziologických a patofyziologických procesech na úrovni buňky i celého organismu.

Links

IAA501630801, research and development project
Name: Mechanismus účinku prokatepsinu D na buňky rakoviny prsu
Investor: Academy of Sciences of the Czech Republic, Mechanism of procathepsin D effect on breast cancer cells
MSM0021622415, plan (intention)
Name: Molekulární podstata buněčných a tkáňových regulací
Investor: Ministry of Education, Youth and Sports of the CR, Molecular basis of cell and tissue regulations