Molecular biology of PCSK9: its role in LDL metabolism

被引：484

作者：

Horton, Jay D.

Cohen, Jonathan C.

Hobbs, Helen H.

机构：

[1] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA

[2] Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75390 USA

[3] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA

来源：

TRENDS IN BIOCHEMICAL SCIENCES | 2007年 / 32卷 / 02期

关键词：

D O I：

10.1016/j.tibs.2006.12.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Proprotein convertase subtilisin-like kexin type 9 (PCSK9) is a newly discovered serine protease that destroys low density lipoprotein (LDL) receptors in liver and thereby controls the level of LDL in plasma. Mutations that increase PCSK9 activity cause hypercholesterolemia and coronary heart disease (CHD); mutations that inactivate PCSK9 have the opposite effect, lowering LDL levels and reducing CHD. Although the mechanism of PCSK9 action is not yet clear, the protease provides a new therapeutic target to lower plasma levels of LDL and prevent CHD.

引用

页码：71 / 77

页数：7

共 44 条

[1] Mutations in PCSK9 cause autosomal dominant hypercholesterolemia [J].

Abifadel, M ;

Varret, M ;

Rabès, JP ;

Allard, D ;

Ouguerram, K ;

Devillers, M ;

Cruaud, C ;

Benjannet, S ;

Wickham, L ;

Erlich, D ;

Derré, A ;

Villéger, L ;

Farnier, M ;

Beucler, I ;

Bruckert, E ;

Chambaz, J ;

Chanu, B ;

Lecerf, JM ;

Luc, G ;

Moulin, P ;

Weissenbach, J ;

Prat, A ;

Krempf, M ;

Junien, C ;

Seidah, NG ;

Boileau, C .

NATURE GENETICS, 2003, 34 (02) :154-156

[2] Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor [J].

Agnello, V ;

Abel, G ;

Elfahal, M ;

Knight, GB ;

Zhang, QX .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (22) :12766-12771

[3]

Allard Delphine, 2005, Hum Mutat, V26, P497, DOI 10.1002/humu.9383

[4] Inhibitors of proprotein convertases [J].

Basak, A .

JOURNAL OF MOLECULAR MEDICINE-JMM, 2005, 83 (11) :844-855

[5] NARC-1/PCSK9 and its natural mutants -: Zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol [J].

Benjannet, S ;

Rhainds, D ;

Essalmani, R ;

Mayne, J ;

Wickham, L ;

Jin, WJ ;

Asselin, MC ;

Hamelin, J ;

Varret, M ;

Allard, D ;

Trillard, M ;

Abifadel, M ;

Tebon, A ;

Attie, AD ;

Rader, DJ ;

Boileau, C ;

Brissette, L ;

Chrétien, M ;

Prat, A ;

Seidah, NG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (47) :48865-48875

[6] The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A-Functional consequences of natural mutations and post-translational modifications [J].

Benjannet, Suzanne ;

Rhainds, David ;

Hamelin, Josee ;

Nassoury, Nasha ;

Seidah, Nabil G. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (41) :30561-30572

[7] Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy [J].

Berge, KE ;

Ose, L ;

Leren, TP .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (05) :1094-1100

[8] Biomedicine - Lowering LDL - Not only how low, but how long? [J].

Brown, MS ;

Goldstein, JL .

SCIENCE, 2006, 311 (5768) :1721-1723

[9] Effect of mutations in the PCSK9 gene on the cell surface LDL receptors [J].

Cameron, J ;

Holla, OL ;

Ranheim, T ;

Kulseth, MA ;

Berge, KE ;

Leren, TP .

HUMAN MOLECULAR GENETICS, 2006, 15 (09) :1551-1558

[10] Low LDL cholesterol in African Americans resulting from frequent nonsense mutations in PCSK9 [J].

Cohen, J ;

Pertsemlidis, A ;

Kotowski, IK ;

Graham, R ;

Garcia, CK ;

Hobbs, HH .

NATURE GENETICS, 2005, 37 (03) :328-328

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