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Table 1 Summary of the 10 genes found in these studies to induce apoptosis when over-expressed. Function, sub-cellular localisations and GO categories of the genes are given. Yellow highlights GO apoptotic activity.

From: Identification and characterisation of human apoptosis inducing proteins using cell-based transfection microarrays and expression analysis

Gene name

Function

Proposed apoptotic hypothesis

Localisation (Swiss-Prot)

GO categories

C22ORF23

Not known

None

Not known

Not known

XBP1

XBP1 binds to the X box of the HLA-DR-alpha promoter (MHC human class II gene) [20] and responds to accumulation of unfolded proteins in the ER [21].

XBP1 increases ER membrane production, this change in intra-cellular balance may trigger apopotosis.

Nuclear

- Immune response

- Nucleus

- Regulation of transcription

- Transcription factor activity

CSTB

The main role of cathepsins is the degradation of protein. Maintenance of appropriate equilibrium between free cysteine proteases and their complexes with inhibitors is crucial for proper functioning of all living systems [23]. Mutations in CSTB result in myoclonus epilepsy [35].

If cathepsins are highly inhibited by CSTB, this could prevent degradation of peptides and proteins, which could stimulate an apoptotic pathway.

Cytoplasmic and nuclear.

- Cysteine protease inhibitor

- Nucleus

MGC5439

Not known

None

Not known

Not known

STK3

STK3 and 4 are involved in Fas mediated apoptosis and are cleaved/activated by CASP3. When stably expressed in HeLa cells, STK3 and 4 highly sensitise the cell to death receptor mediated apoptosis by accelerating CASP3 activation [19].

These findings suggest that STK3 and STK4 play a role in apoptosis both upstream and downstream of caspase activation [16].

Cytoplasmic (By similarity)

- Protein kinase CK2 activity

- Serine/threonine kinase activity

- cAMP-dependent kinase activity

- Cytoplasm

- Smino acid phosphorylation

- Tyrosine kinase activity

- Transferase activity

- Apoptosis

- ATP binding

- Signal transduction

ACO1

Transferrin receptor (Tfr) is a membrane receptor that transports iron into the cell via endocytosis. Free iron is toxic to cells, but not if bound to ferritin. ACO1 (IREBP – IRE binding protein) [25] represses ferritin translation and increases Tfr translation [24].

Over-expression of ACO-1 will cause increased Tfr and excess iron within the cell. Ferritin translation is repressed by ACO1 so the excess free iron will be unbound. Excess intracellular iron induces apoptosis in cells.

Cytoplasmic

- Lyase activity

- Tricarboxylic acid cycle

- Aconitate hydratase activity

- Cytoplasm

- Negative regulation of translation

- Metabolism

- RNA binding

MLLT11

Involved in acute leukemias by a chromosomal translocation. MMLT11 could possibly be a cytokine [36].

None

Not known

- Cell growth and/or maintenance

CCBP2

CCBP2 is a promiscuous receptor [37], binds to SCYA2/MCP-1, SCY3/MIP-1-ALPHA, SCYA5/RANTES AND SCYA7/MCP-3. CCBP2 is expressed in the lymphatic endothelium, a subset of vascular tumors [37] and melanoma cells [38].

None

Integral membrane protein

- Immune response

- Integral to plasma membrane

- Development

- G-protein coupled receptor

- Chemotaxis

- C-C chemokine receptor activity

- Rhodopsin-like receptor activity

LOC134285

No information

  

-Receptor activity

EXOC7 (KIAA1067)

EXOC7 is 1 of 8 subunits of the exocyst which transports material within membrane bound vesicles inside the cell to the surface. The intracellular vesicles fuse with the plasma membrane and contents are released to the exterior [26].

Over-expression of EXOC7 may cause excessive removal of internal cell contents and cause apoptosis to occur.

Cytosolic

- Intracellular protein transport

- Exocytosis

- Exocyst

- Protein transporter activity