6g6s

Structural highlights

Function

[ACINU_HUMAN] Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells.^{[1] [2] [3] [4] [5]}

References

1. ↑ Sahara S, Aoto M, Eguchi Y, Imamoto N, Yoneda Y, Tsujimoto Y. Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation. Nature. 1999 Sep 9;401(6749):168-73. doi: 10.1038/43678. PMID:10490026 doi:http://dx.doi.org/10.1038/43678
2. ↑ Schwerk C, Prasad J, Degenhardt K, Erdjument-Bromage H, White E, Tempst P, Kidd VJ, Manley JL, Lahti JM, Reinberg D. ASAP, a novel protein complex involved in RNA processing and apoptosis. Mol Cell Biol. 2003 Apr;23(8):2981-90. PMID:12665594
3. ↑ Jang SW, Yang SJ, Ehlen A, Dong S, Khoury H, Chen J, Persson JL, Ye K. Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1. Cancer Res. 2008 Jun 15;68(12):4559-70. doi: 10.1158/0008-5472.CAN-08-0021. PMID:18559500 doi:http://dx.doi.org/10.1158/0008-5472.CAN-08-0021
4. ↑ Michelle L, Cloutier A, Toutant J, Shkreta L, Thibault P, Durand M, Garneau D, Gendron D, Lapointe E, Couture S, Le Hir H, Klinck R, Elela SA, Prinos P, Chabot B. Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators. Mol Cell Biol. 2012 Mar;32(5):954-67. doi: 10.1128/MCB.06130-11. Epub 2011 Dec, 27. PMID:22203037 doi:http://dx.doi.org/10.1128/MCB.06130-11
5. ↑ Murachelli AG, Ebert J, Basquin C, Le Hir H, Conti E. The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex. Nat Struct Mol Biol. 2012 Mar 4;19(4):378-86. doi: 10.1038/nsmb.2242. PMID:22388736 doi:10.1038/nsmb.2242