KEGG PATHWAY: ko04214

PATHWAY: ko04214

Entry

ko04214                     Pathway

Name

Apoptosis - fly

Description

Apoptosis, or programmed cell death, is a critical factor in homeostasis in all multicellular organisms, playing a crucial role in removing excess unwanted cells without stimulation of an immune response. Caspases are the central components of the apoptotic response. In Drosophila, Dark promotes activation of the initiator caspase Dronc. Drosophila inhibitor of apoptosis protein 1 (DIAP1) inhibits Dronc and the effector caspases Drice and Dcp-1. RHG family proteins such as Rpr, Hid, Grim, Sickle, and Jafrac-2 promote cell death, in part by disrupting DIAP1's ability to inhibit caspase activity. Proapoptotic proteins such as caspases and RHG proteins are regulated through multiple pathways. The Drosophila steroid hormone ecdysone mediates cell death by controling the up-regulation of a number of proapoptotic genes. Cytotoxic stress such as DNA damage can activate P53, which in turn induces the expression of RHG genes. Eiger can initiate cell death through an IAP-sensitive cell death pathway via JNK signaling. Hid, a member of the RHG family, is negatively regulated by the epidermal growth factor (EGF) receptor-dependent survival signaling and positively regulated by the tumor suppressors Hippo, Salvador, and Warts.

Class

Cellular Processes; Cell growth and death

Pathway map

ko04214

Apoptosis - fly

Orthology

K01527

EGD1, BTF3; nascent polypeptide-associated complex subunit beta

K02084

APAF1; apoptotic protease-activating factor

K02174

BR-C; broad-complex core protein

K02561

BOK; Bcl-2-related ovarian killer protein

K03175

TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]

K03262

EIF5; translation initiation factor 5

K03386

PRDX2_4, ahpC; peroxiredoxin 2/4 [EC:1.11.1.24]

K04361

EGFR, ERBB1; epidermal growth factor receptor [EC:2.7.10.1]

K04365

BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04371

ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K04374

ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4

K04397

CASP7; caspase 7 [EC:3.4.22.60]

K04398

CASP8; caspase 8 [EC:3.4.22.61]

K04404

MAP3K7IP2, TAB2; TAK1-binding protein 2

K04412

STK3, MST2; serine/threonine kinase 3

K04426

MAP3K5, ASK1; mitogen-activated protein kinase kinase kinase 5 [EC:2.7.11.25]

K04427

MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]

K04431

MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]

K04440

JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]

K04448

JUN; transcription factor AP-1

K04725

XIAP, BIRC4; E3 ubiquitin-protein ligase XIAP [EC:2.3.2.27]

K04727

AIFM1, PDCD8; apoptosis-inducing factor 1 [EC:1.-.-.-]

K04728

ATM, TEL1; serine-protein kinase ATM [EC:2.7.11.1]

K05770

TSPO, BZRP; translocator protein

K06030

MFN2, FZO1; mitofusin 2 [EC:3.6.5.-]

K06640

ATR; serine/threonine-protein kinase ATR [EC:2.7.11.1]

K07611

LMNB; lamin B

K07827

KRAS, KRAS2; GTPase KRas

K07870

RHOT1, ARHT1; mitochondrial Rho GTPase 1 [EC:3.6.5.-]

K08669

HTRA2, PRSS25; HtrA serine peptidase 2 [EC:3.4.21.108]

K08738

CYC; cytochrome c

K08791

LATS1_2, Wts; serine/threonine-protein kinase LATS1/2 [EC:2.7.11.1]

K08860

EIF2AK3, PERK; eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1]

K09031

FOSLN; fos-like antigen, invertebrate

K09428

ELF1_2_4; E74-like factor 1/2/4

K09848

TRAF4; TNF receptor-associated factor 4

K10149

TP63; tumor protein p63

K10586

BIRC6, BRUCE; baculoviral IAP repeat-containing protein 6 (apollon) [EC:2.3.2.23]

K14030

NR2B4, usp; nuclear receptor subfamily 2 group B member 4

K14034

NR1H1, EcR; ecdysone receptor

K16678

EGR; eiger

K16679

WGN; wengen

K16686

SAV1, Sav; scaffold protein salvador

K16736

BAN; bantam

K17065

DNM1L; dynamin 1-like protein [EC:3.6.5.5]

K20008

DCP1; death caspase-1 [EC:3.4.22.-]

K20009

DRONC; caspase Dronc [EC:3.4.22.-]

K20010

STRICA; Ser/Thr-rich caspase [EC:3.4.22.-]

K20014

RPR; cell death protein rpr

K20015

EIP93F; ecdysone-induced protein 93F, isoform B

K20016

HID; cell death protein hid

K20017

BUFFY; Bcl-2 family protein

K20018

GRIM; cell death protein Grim

K20019

SKL; IAP-inhibitory protein Sickle

K20216

DUSP10; dual specificity phosphatase 10 [EC:3.1.3.16 3.1.3.48]

K24070

PARP1; poly [ADP-ribose] polymerase 1

Compound

C00477

Ecdysone

Reference

PMID:16842034

Authors

Hay BA, Guo M

Title

Caspase-dependent cell death in Drosophila.

Journal

Annu Rev Cell Dev Biol 22:623-50 (2006)
DOI:10.1146/annurev.cellbio.21.012804.093845

Reference

PMID:15573123

Authors

Hay BA, Huh JR, Guo M

Title

The genetics of cell death: approaches, insights and opportunities in Drosophila.

Journal

Nat Rev Genet 5:911-22 (2004)
DOI:10.1038/nrg1491

Reference

PMID:15082313

Authors

Kumar S, Cakouros D

Title

Transcriptional control of the core cell-death machinery.

Journal

Trends Biochem Sci 29:193-9 (2004)
DOI:10.1016/j.tibs.2004.02.001

Reference

PMID:25991373

Authors

Fuchs Y, Steller H

Title

Live to die another way: modes of programmed cell death and the signals emanating from dying cells.

Journal

Nat Rev Mol Cell Biol 16:329-44 (2015)
DOI:10.1038/nrm3999

Reference

PMID:25668151

Authors

Arya R, White K

Title

Cell death in development: Signaling pathways and core mechanisms.

Journal

Semin Cell Dev Biol 39:12-9 (2015)
DOI:10.1016/j.semcdb.2015.02.001

Reference

PMID:14744432

Authors

Danial NN, Korsmeyer SJ

Title

Cell death: critical control points.

Journal

Cell 116:205-19 (2004)
DOI:10.1016/S0092-8674(04)00046-7

Reference

PMID:12006672

Authors

Gorski S, Marra M

Title

Programmed cell death takes flight: genetic and genomic approaches to gene discovery in Drosophila.

Journal

Physiol Genomics 9:59-69 (2002)
DOI:10.1152/physiolgenomics.00114.2001

Reference

PMID:12072176

Authors

Richardson H, Kumar S

Title

Death to flies: Drosophila as a model system to study programmed cell death.

Journal

J Immunol Methods 265:21-38 (2002)
DOI:10.1016/S0022-1759(02)00068-6

Reference

PMID:21338340

Authors

Kuranaga E

Title

Caspase signaling in animal development.

Journal

Dev Growth Differ 53:137-48 (2011)
DOI:10.1111/j.1440-169X.2010.01237.x

Reference

PMID:20978240

Authors

Bergmann A, Steller H

Title

Apoptosis, stem cells, and tissue regeneration.

Journal

Sci Signal 3:re8 (2010)
DOI:10.1126/scisignal.3145re8

Reference

PMID:15520809

Authors

Riedl SJ, Shi Y

Title

Molecular mechanisms of caspase regulation during apoptosis.

Journal

Nat Rev Mol Cell Biol 5:897-907 (2004)
DOI:10.1038/nrm1496

Reference

PMID:14996492

Authors

Igaki T, Miura M

Title

Role of Bcl-2 family members in invertebrates.

Journal

Biochim Biophys Acta 1644:73-81 (2004)
DOI:10.1016/j.bbamcr.2003.09.007

Reference

PMID:26679112

Authors

Clavier A, Rincheval-Arnold A, Colin J, Mignotte B, Guenal I

Title

Apoptosis in Drosophila: which role for mitochondria?

Journal

Apoptosis 21:239-51 (2016)
DOI:10.1007/s10495-015-1209-y

Reference

PMID:20950655

Authors

Abdelwahid E, Rolland S, Teng X, Conradt B, Hardwick JM, White K

Title

Mitochondrial involvement in cell death of non-mammalian eukaryotes.

Journal

Biochim Biophys Acta 1813:597-607 (2011)
DOI:10.1016/j.bbamcr.2010.10.008

Reference

PMID:25299777

Authors

Demay Y, Perochon J, Szuplewski S, Mignotte B, Gaumer S

Title

The PERK pathway independently triggers apoptosis and a Rac1/Slpr/JNK/Dilp8 signaling favoring tissue homeostasis in a chronic ER stress Drosophila model.

Journal

Cell Death Dis 5:e1452 (2014)
DOI:10.1038/cddis.2014.403

Reference

PMID:15657059

Authors

Kilpatrick ZE, Cakouros D, Kumar S

Title

Ecdysone-mediated up-regulation of the effector caspase DRICE is required for hormone-dependent apoptosis in Drosophila cells.

Journal

J Biol Chem 280:11981-6 (2005)
DOI:10.1074/jbc.M413971200

Reference

PMID:12070100

Authors

Yu SY, Yoo SJ, Yang L, Zapata C, Srinivasan A, Hay BA, Baker NE

Title

A pathway of signals regulating effector and initiator caspases in the developing Drosophila eye.

Journal

Development 129:3269-78 (2002)

Reference

PMID:10074440

Authors

McNeill H, Downward J

Title

Apoptosis: Ras to the rescue in the fly eye.

Journal

Curr Biol 9:R176-9 (1999)
DOI:10.1016/S0960-9822(99)80107-9

Reference

PMID:19223855

Authors

Narasimamurthy R, Geuking P, Ingold K, Willen L, Schneider P, Basler K

Title

Structure-function analysis of Eiger, the Drosophila TNF homolog.

Journal

Cell Res 19:392-4 (2009)
DOI:10.1038/cr.2009.16

Reference

PMID:23408884

Authors

Liu B, Behura SK, Clem RJ, Schneemann A, Becnel J, Severson DW, Zhou L

Title

P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster.

Journal

PLoS Pathog 9:e1003137 (2013)
DOI:10.1371/journal.ppat.1003137

Reference

PMID:12198495

Authors

Kuranaga E, Kanuka H, Igaki T, Sawamoto K, Ichijo H, Okano H, Miura M

Title

Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila.

Journal

Nat Cell Biol 4:705-10 (2002)
DOI:10.1038/ncb842

Reference

PMID:19330035

Authors

Creagh EM, Brumatti G, Sheridan C, Duriez PJ, Taylor RC, Cullen SP, Adrain C, Martin SJ

Title

Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival.

Journal

PLoS One 4:e5055 (2009)
DOI:10.1371/journal.pone.0005055

Reference

PMID:19554451

Authors

Bilak A, Su TT

Title

Regulation of Drosophila melanogaster pro-apoptotic gene hid.

Journal

Apoptosis 14:943-9 (2009)
DOI:10.1007/s10495-009-0374-2

Related
pathway

ko04391

Hippo signaling pathway - fly

DBGET integrated database retrieval system