| Category | Description | Evidence/Source |
|---|---|---|
| Gene Identity | **cct-8** in *Caenorhabditis elegans* encodes **T-complex protein 1 subunit theta (CCT-8/CCT8)**, one of the eight distinct subunits of the cytosolic **TRiC/CCT chaperonin**. This matches the theta subunit annotation and places the protein in the conserved TCP-1 chaperonin family. | (pqac-00000011, pqac-00000013, pqac-00000017) |
| Protein Function | CCT-8 functions as a **structural and functional subunit of the ATP-dependent TRiC/CCT folding machine**, which promotes folding of obligate cytoskeletal substrates such as **actin and tubulin** and also assists folding/assembly of additional cytosolic proteins, including many WD40-repeat proteins. The complex facilitates folding rather than catalyzing a classic small-molecule enzymatic transformation. | (pqac-00000011, pqac-00000012, pqac-00000013, pqac-00000014) |
| Subcellular Localization | TRiC/CCT is a **cytosolic/cytoplasmic chaperonin complex** in eukaryotic cells; therefore CCT-8’s primary site of action is the **cytosol**, where newly synthesized and metastable cytosolic proteins are folded. | (pqac-00000006, pqac-00000007, pqac-00000008, pqac-00000009) |
| Biological Processes | In *C. elegans*, cct-8 supports **proteostasis**, resistance to **proteotoxic stress**, maintenance of protein folding capacity during **aging**, and suppression of toxic protein aggregation. Overexpression of cct-8 increases TRiC/CCT assembly and improves organismal protein homeostasis. | (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000004) |
| Biological Processes | cct-8 also contributes to **germline stability/proliferative cell function** and is linked to maintenance of tissue fitness under stress. Adult knockdown of CCT subunits decreases germ cell numbers, while high TRiC/CCT levels are important for proliferating cells and germline integrity. | (pqac-00000025, pqac-00000029) |
| Pathway Involvement | cct-8 is functionally required for lifespan extension in major *C. elegans* longevity paradigms, including **reduced insulin/IGF-1 signaling** (**daf-2**), **dietary restriction** (**eat-2**), and **germline-loss signaling** (**glp-1**). Knockdown of cct-8 shortens the extended lifespan of these long-lived backgrounds, indicating that TRiC/CCT-dependent proteostasis is a shared downstream requirement. | (pqac-00000022, pqac-00000023) |
| Pathway Involvement | cct-8-mediated lifespan extension is at least partly **HSF-1-independent**: cct-8 overexpression can remain beneficial even when **hsf-1** is knocked down, suggesting that boosting TRiC/CCT assembly can bypass some dependence on the canonical heat-shock transcriptional program. | (pqac-00000001, pqac-00000022, pqac-00000024) |
| Key Phenotypes | **Somatic overexpression** of cct-8 extends *C. elegans* lifespan by about **20% under normal conditions** and by roughly **20–40% under mild heat stress/heat-stress paradigms**, consistent with improved proteostasis in adulthood. | (pqac-00000001, pqac-00000004) |
| Key Phenotypes | cct-8 overexpression reduces **polyQ67 aggregate burden**, improves **motility**, and ameliorates proteotoxic phenotypes in worm models of **Huntington-like polyglutamine toxicity** without reducing total polyQ protein levels, consistent with improved folding/aggregation control rather than reduced expression. | (pqac-00000002, pqac-00000003, pqac-00000026, pqac-00000028) |
| Key Phenotypes | Loss or downregulation of TRiC/CCT activity, including cct-8 perturbation, compromises proteostasis and promotes aggregation of disease-linked proteins; neuronal-specific CCT downregulation is sufficient to enhance **neuronal polyQ67 aggregation**. | (pqac-00000027, pqac-00000038) |
| Subunit-Specific Properties | Within TRiC/CCT, CCT-8 belongs to the **low-ATPase / low-ATP-affinity CCT6 hemisphere** (with CCT1/3/6/8). It retains bound **ADP** unusually strongly, has **slow ADP off-rates**, and may contribute less to ATP consumption than high-affinity subunits, implying a more specialized regulatory role in the ATPase cycle. | (pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000030) |
| Subunit-Specific Properties | CCT-8 contributes to **allosteric cooperativity** and **complex assembly**, potentially via N-terminal features that function partly independently of ATP hydrolysis. These properties suggest that cct-8 is not merely interchangeable with other subunits but helps define TRiC/CCT architecture and regulation. | (pqac-00000019, pqac-00000031) |
| Subunit-Specific Properties | CCT-8 also participates directly in **substrate binding contacts**. Structural studies indicate many substrates contact CCT8, and **actin** and **tubulin** each make contacts with CCT8-containing apical domains during the folding cycle, helping position/stabilize folding intermediates. | (pqac-00000020, pqac-00000030, pqac-00000034) |
| Structural Context | The eight TRiC/CCT subunits occupy **fixed positions** within each ring; proposed arrangements place CCT8 at a defined site and indicate it may participate in **homotypic inter-ring contacts**, supporting its contribution to complex architecture as well as folding function. | (pqac-00000032, pqac-00000033, pqac-00000035) |


*Table: This table summarizes the verified functional annotation of *C. elegans* cct-8/CCT-8 as the theta subunit of the TRiC/CCT chaperonin. It highlights molecular function, localization, pathway links, phenotypes, and subunit-specific properties most relevant to proteostasis, aging, and polyQ aggregation.*