Table 6.
Functional studies of subunits of the INO80 complex in PDAC (or other cancers).
| INO80 Subfamily (INO 80 Complex) | |
|---|---|
| Subunit | Protein Name/Functional Studies |
| INO80 | INO80 Complex ATPase Subunit. See Section 4.4.1. |
| ACTL6A | Actin Like 6A. See Section 4.5.2. |
| ACTR5 (INO80M) * | Actin Related Protein 5. Increased in CRC [226], decreased in pancreatic tumors [227]. ACTR5 facilitates binding of INO80 complex to DNA, INO80 complexes lacking ACTR5 have reduced ATPase and chromatin remodeling activities in vitro [228]. Involved in nucleosome recognition [219]. |
| ACTR8 (INO80N) * | Actin Related Protein 8. ACTR8 facilitates binding of INO80 complex to DNA, INO80 complexes lacking ACTR8 have reduced ATPase and chromatin remodeling activities in vitro [228]. |
| INO80B * | INO80 Complex Subunit B. Regulates INO80 ATPase activity in vitro [219,229]. |
| INO80C * | INO80 Complex Subunit C. Tumor suppressor role. See Section 4.4.2. |
| RUVBL1 (RVB1, Tip49a, pontin)/RUVBL2 (RVB2, Tip49b, reptin) * | RuvB Like AAA ATPase 1/2. RUVBL1: Required for efficient mitosis and proliferation of cells [230]. Expression is increased in HCC, CRC and other cancers, involved in cell invasion and EMT. Interacts with oncogene c-MYC and β-catenin. Roles in cell growth and viability [231,232,233,234,235,236,237,238]. In a mouse model of liver cancer, accumulation of E2f1 recruits the RUVBL1/RUVBL2 complex that opens the chromatin conformation at E2f target genes and amplifies the E2f transcriptional response during cancer progression. Can function as a separate complex, not involved in INO80 subfamilies [231]. Cytoplasmic RUVBL1 interacts with actin filaments at cell protrusions and thus promotes invasiveness and migration of PDAC cells [239], which is a role independent of its chromatin remodeling [240]. No other data in PDAC. RUVBL2: Expression is increased in HCC, CRC. Interacts with oncogene c-MYC and β-catenin. Roles in cell growth and viability [231,232,233,235,240,241,242,243]. Interacts with mutant p53 [244]. |
| YY1 | YY1 Transcription Factor. A zinc finger transcription factor, that can either repress or activate gene transcription by recruiting different cofactors. YY1 expression is increased in PDAC [245,246], higher YY1 levels are associated with oncogenic KRASG12D status in pancreatic cancer cell lines and patient samples [245]. YY1 regulates the expression of Snail1 and VEGF, promoting EMT and angiogenesis [247,248]. Conflicting results reporting its role as a tumor suppressor in inhibiting the migration, invasiveness and proliferation in PDAC cells [249,250,251]. Other studies also report a dual tumor suppressor and oncogenic role [247,252,253,254,255]. |
| MCRS1 (MSP58) * | Microspherule Protein 1. Promoted proliferation, invasion and metastasis of lung cancer cells [256,257] and proliferation and tumor growth of colon carcinoma cells [258]. Increased in CRC [258,259,260]. Involved in mTORC1 activation, thus having an oncogenic role [259]. |
| NFRKB | Nuclear Factor Related to KappaB Binding Protein. NFRKB binds to UCH37, disrupting the active site for ubiquitin binding and inhibiting its function [261]. |
| UCHL5 (UCH37) * | Ubiquitin C-Terminal Hydrolase L5. UCHL5 deubiquitylase-dual roles component of INO80 and 26S proteasome [261]. Implicated in cancer [262,263]. Promotes Hedgehog signaling and TGFb-1 signaling [264,265]. |
| TFPT * | TCF3 Fusion Partner. Translocations are involved in B-cell precursor acute lymphoblastic leukemia [266] |
Note: * No/limited mechanistic studies in pancreatic cancer.