Identification of a novel p73 protein binding partner, breast cancer associated 3 (BCA3), in gynecological cancer
Bibliographic record
Abstract
The candidate tumor suppressor gene, p73 is a member of p53 family protein. It was predicted to encode a protein with significant similarity to p53. p73 was mapped to the minimal chromosomal region of 1p36 that is recurrently deleted in many types of cancers such as neuroblastoma, breast cancer, squamous cell carcinoma and B-cell lymphoma. Unlike p53, somatic mutation of p73 gene is extremely rare. p73 exists in two forms: the N-terminal transactivation domain containing form (TAp73) and an isoform without the transactivation domain (DNp73). TAp73 exhibits growth inhibitory, tumor suppressive and pro-apoptotic functions while DNp73 promotes oncogenic activity and abolishes the functions of TAp73. Evidence from our previous finding revealed an association between p73 expression and radiosensitivity of cervical cancers and suggested that p73 might play an important role in controlling cellular radiosensitivity. In the present study, we aimed to identify cellular proteins that interact with p73 and contribute to the development of gynecological cancer. Using yeast two hybrid screening with DNp73 as a bait, we identified a Breast Cancer Associated gene 3 (BCA3) as a novel binding partner of p73. BCA3 gene is a novel protein which plays an important role in substrate localization, transcriptional regulation as well as actin cytoskeleton remodeling. Coimmunoprecipitation experiment confirmed the interaction of DNp73 and BCA3 in HEK293 cells whereas BCA3 did not interact with p53. Interestingly, differential binding affinity with BCA3 was detected between TAp73 and DNp73 isoforms. Coexpression of DNp73 and BCA3 showed colocalization of both proteins in the perinuclear region in cervical cancer cell line (SiHa). Furthermore, with RT-PCR using specific primers performed on 7 cervical cancer cell lines, 4 normal cervix cell lines, 10 ovarian cancer cell lines, 7 normal ovary cell lines and 3 endometrial cancer cell lines, BCA3 was expressed at various expression levels in most cell lines tested. Low or no BCA3 expression was detected in 4 ovarian cancer cell lines and 3 endometrial cancer cell lines. In summary, BCA3 is a novel protein binding partner of p73. It interacts with p73 but not p53 suggesting that BCA3 particularly interacts with p73 which may ultimately influence p73 functions. The differential binding affinity of BCA3 among TAp73 and DNp73 implicating that BCA3 might play a unique role in regulating the function of p73 isoforms. Further studies on the molecular mechanism between p73 and BCA3 may give insight into tumor suppressor function of p73 in gynecological cancer.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".