The BCL-2 Family Member BID Plays a Role During Embryonic Development in Addition to Its BH3-only Protein Function by Acting in Parallel to BAX, BAK and BOK

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2022 Jun 27

PMID 35758142

Authors

Francine S Ke

Steven Holloway

Rachel T Uren

Agnes W Wong

Melissa H Little

Ruth M Kluck

Anne K Voss

Andreas Strasser

Affiliations

Soon will be listed here.

Abstract

The intrinsic apoptosis pathway, regulated by the BCL-2 protein family, is essential for embryonic development. Using mice lacking all known apoptosis effectors, BAX, BAK and BOK, we have previously defined the processes during development that require apoptosis. Rare Bok Bax Bak triple knockout (TKO) mice developed to adulthood and several tissues that were thought to require apoptosis during development appeared normal. This raises the question if all apoptosis had been abolished in the TKO mice or if other BCL-2 family members could act as effectors of apoptosis. Here, we investigated the role of BID, generally considered to link the extrinsic and intrinsic apoptosis pathways, acting as a BH3-only protein initiating apoptosis upstream of BAX and BAK. We found that Bok Bax Bak Bid quadruple knockout (QKO) mice have additional developmental anomalies compared to TKO mice, consistent with a role of BID, not only upstream but also in parallel to BAX, BAK and BOK. Mitochondrial experiments identified a small cytochrome c-releasing activity of full-length BID. Collectively, these findings suggest a new effector role for BID in the intrinsic apoptosis pathway.

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References

Bouillet P, Cory S, Zhang L, Strasser A, Adams J . Degenerative disorders caused by Bcl-2 deficiency prevented by loss of its BH3-only antagonist Bim. Dev Cell. 2001; 1(5):645-53. DOI: 10.1016/s1534-5807(01)00083-1. View

Kaufmann T, Tai L, Ekert P, Huang D, Norris F, Lindemann R . The BH3-only protein bid is dispensable for DNA damage- and replicative stress-induced apoptosis or cell-cycle arrest. Cell. 2007; 129(2):423-33. DOI: 10.1016/j.cell.2007.03.017. View

Ke F, Vanyai H, Cowan A, Delbridge A, Whitehead L, Grabow S . Embryogenesis and Adult Life in the Absence of Intrinsic Apoptosis Effectors BAX, BAK, and BOK. Cell. 2018; 173(5):1217-1230.e17. DOI: 10.1016/j.cell.2018.04.036. View

Taniguchi H, Kitaoka T, Gong H, Amemiya T . Apoptosis of the hyaloid artery in the rat eye. Ann Anat. 1999; 181(6):555-60. DOI: 10.1016/S0940-9602(99)80061-2. View

Ke F, Holloway S, Uren R, Wong A, Little M, Kluck R . The BCL-2 family member BID plays a role during embryonic development in addition to its BH3-only protein function by acting in parallel to BAX, BAK and BOK. EMBO J. 2022; 41(15):e110300. PMC: 9340487. DOI: 10.15252/embj.2021110300. View

Youle R, Strasser A . The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2007; 9(1):47-59. DOI: 10.1038/nrm2308. View

Koseki C, Herzlinger D, Al-Awqati Q . Apoptosis in metanephric development. J Cell Biol. 1992; 119(5):1327-33. PMC: 2289732. DOI: 10.1083/jcb.119.5.1327. View

Bingham C, Bulman M, Ellard S, Allen L, Lipkin G, Hoff W . Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease. Am J Hum Genet. 2000; 68(1):219-24. PMC: 1234916. DOI: 10.1086/316945. View

Sorenson C, Rogers S, Korsmeyer S, Hammerman M . Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. Am J Physiol. 1995; 268(1 Pt 2):F73-81. DOI: 10.1152/ajprenal.1995.268.1.F73. View

10.

Kim J, Lee G, Tisher C, Madsen K . Role of apoptosis in development of the ascending thin limb of the loop of Henle in rat kidney. Am J Physiol. 1996; 271(4 Pt 2):F831-45. DOI: 10.1152/ajprenal.1996.271.4.F831. View

11.

Singh R, Letai A, Sarosiek K . Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol. 2019; 20(3):175-193. PMC: 7325303. DOI: 10.1038/s41580-018-0089-8. View

12.

Jost P, Grabow S, Gray D, McKenzie M, Nachbur U, Huang D . XIAP discriminates between type I and type II FAS-induced apoptosis. Nature. 2009; 460(7258):1035-9. PMC: 2956120. DOI: 10.1038/nature08229. View

13.

Robin A, Kumar K, Westphal D, Wardak A, Thompson G, Dewson G . Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction. Cell Death Dis. 2015; 6:e1809. PMC: 4650713. DOI: 10.1038/cddis.2015.141. View

14.

Smith P, Dunn M . Duplication of the upper urinary tract. Ann R Coll Surg Engl. 1979; 61(4):281-6. PMC: 2492178. View

15.

Bolar N, Golzio C, Zivna M, Hayot G, Van Hemelrijk C, Schepers D . Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia. Am J Hum Genet. 2016; 99(1):174-87. PMC: 5005467. DOI: 10.1016/j.ajhg.2016.05.028. View

16.

Ren D, Tu H, Kim H, Wang G, Bean G, Takeuchi O . BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. Science. 2010; 330(6009):1390-3. PMC: 3163443. DOI: 10.1126/science.1190217. View

17.

Billen L, Shamas-Din A, Andrews D . Bid: a Bax-like BH3 protein. Oncogene. 2009; 27 Suppl 1:S93-104. DOI: 10.1038/onc.2009.47. View

18.

Kreidberg J, Sariola H, LORING J, Maeda M, Pelletier J, Housman D . WT-1 is required for early kidney development. Cell. 1993; 74(4):679-91. DOI: 10.1016/0092-8674(93)90515-r. View

19.

Kamada S, Shimono A, Shinto Y, Tsujimura T, Takahashi T, Noda T . bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine. Cancer Res. 1995; 55(2):354-9. View

20.

Ito M, Yoshioka M . Regression of the hyaloid vessels and pupillary membrane of the mouse. Anat Embryol (Berl). 1999; 200(4):403-11. DOI: 10.1007/s004290050289. View