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PMID: 16594896 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

HIV protease cleaves poly(A)-binding protein.

The Biochemical journal ·Vol. 396 ·No. 2 ·2006-06-01 ·Pages 219-26

Alvarez E, Castelló A, Menéndez-Arias L, Carrasco L

Abstract

The PABP [poly(A)-binding protein] is able to interact with the 3' poly(A) tail of eukaryotic mRNA, promoting its translation. Cleavage of PABP by viral proteases encoded by several picornaviruses and caliciviruses plays a role in the abrogation of cellular protein synthesis. We report that infection of MT-2 cells with HIV-1 leads to efficient proteolysis of PABP. Analysis of PABP integrity was carried out in BHK-21 (baby-hamster kidney) and COS-7 cells upon individual expression of the protease from several members of the Retroviridae family, e.g. MoMLV (Moloney murine leukaemia virus), MMTV (mouse mammary tumour virus), HTLV-I (human T-cell leukaemia virus type I), SIV (simian immunodeficiency virus), HIV-1 and HIV-2. Moreover, protease activity against PABP was tested in a HeLa-cell-free system. Only MMTV, HIV-1 and HIV-2 proteases were able to cleave PABP in the absence of other viral proteins. Purified HIV-1 and HIV-2 proteases cleave PABP1 directly at positions 237 and 477, separating the two first RNA-recognition motifs from the C-terminal domain of PABP. An additional cleavage site located at position 410 was detected for HIV-2 protease. These findings indicate that some retroviruses may share with picornaviruses and caliciviruses the capacity to proteolyse PABP.

MeSH Terms
Amino Acid Sequence Animals Aspartic Acid Endopeptidases/metabolism COS Cells Cells, Cultured Chlorocebus aethiops Cricetinae Eukaryotic Initiation Factor-4G/metabolism HIV Infections/metabolism HIV Protease/metabolism HeLa Cells Humans Hydrolysis Mammary Tumor Virus, Mouse/enzymology,metabolism Mice Models, Genetic Molecular Sequence Data Moloney murine leukemia virus/enzymology,metabolism Poly(A)-Binding Proteins/metabolism Recombinant Proteins/genetics,metabolism Retroviridae Proteins/metabolism,pharmacology Transfection
Chemicals
EIF4G1 protein, human EIF4G2 protein, human Eukaryotic Initiation Factor-4G Poly(A)-Binding Proteins Recombinant Proteins Retroviridae Proteins Aspartic Acid Endopeptidases HIV Protease p16 protease, Human immunodeficiency virus 2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Alvarez Enrique
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain. ealvarez@cnb.uam.es
Castelló Alfredo
Menéndez-Arias Luis
Carrasco Luis
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
Published
2006-06-01
Pages
219-26
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1462710
Subset
IM
Corrections
CommentIn
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