PHAPI, CAS, and Hsp70 promote apoptosome formation by preventing Apaf-1 aggregation and enhancing nucleotide exchange on Apaf-1 Journal Article
| Authors: | Kim, H. E.; Jiang, X.; Du, F.; Wang, X. |
| Article Title: | PHAPI, CAS, and Hsp70 promote apoptosome formation by preventing Apaf-1 aggregation and enhancing nucleotide exchange on Apaf-1 |
| Abstract: | During apoptosis, cytochrome c is released from mitochondria to the cytosol, where it binds Apaf-1. The Apaf-1/cytochrome c complex then oligomerizes either into heptameric caspase-9-activating apoptosome, which subsequently activates caspase-3 and caspase-7, or bigger inactive aggregates, depending on the availability of nucleotide dATP/ATP. A tumor suppressor protein, PHAPI, enhances caspase-9 activation by promoting apoptosome formation through an unknown mechanism. We report here the identification of cellular apoptosis susceptibility protein (CAS) and heat shock protein 70 (Hsp70) as mediators of PHAPI activity. PHAPI, CAS, and Hsp70 function together to accelerate nucleotide exchange on Apaf-1 and prevent inactive Apaf-1/cytochrome c aggregation. CAS expression is induced by multiple apoptotic stimuli including UV irradiation. Knockdown of CAS by RNA interference (RNAi) in cells attenuates apoptosis induced by UV light and causes endogenous Apaf-1 to form aggregates. These studies indicated that PHAPI, CAS, and Hsp70 play an important regulatory role during apoptosis. © 2008 Elsevier Inc. All rights reserved. |
| Keywords: | human cell; protein function; ultraviolet radiation; protein analysis; apoptosis; rna interference; enzyme activation; hela cells; regulatory mechanism; intracellular signaling peptides and proteins; cellcycle; caspase 9; heat shock protein 70; tumor suppressor protein; hsp70 heat-shock proteins; apoptosome; ultraviolet irradiation; cytochrome c; nucleotides; protein aggregation; nucleotide transport; apoptotic protease activating factor 1; cellular apoptosis susceptibility protein; tumor suppressor protein phapi; apoptosomes; apoptotic protease-activating factor 1 |
| Journal Title: | Molecular Cell |
| Volume: | 30 |
| Issue: | 2 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2008-04-25 |
| Start Page: | 239 |
| End Page: | 247 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2008.03.014 |
| PUBMED: | 18439902 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 28" - "Export Date: 17 November 2011" - "CODEN: MOCEF" - "Source: Scopus" |
