Polybromo 1 Proteins (PBRM1)

Human Polybromo 1 (PBRM1) interaction partners

1. The biochemical and mutational analyses have identified bromodomain, BD4 as being critically important for maintaining proper PBRM1 function and demonstrate that BD4 mutations increase clear cell renal cell carcinoma cell growth.

2. Decreased expression of PBRM1 is correlated with poor prognosis and advanced clinicopathological features in patients with renal cell carcinoma (RCC).

3. we show a strong relationship between the expression profiles of PBRM1, BAP1 and SETD2 in ccRCC suggesting reciprocal synergy effects in the context of tumor suppression.

4. In intrahepatic cholangiocarcinoma retained expression of BAP-1 and PBRM-1, and an overexpression of S100P are related to a poor prognosis.

5. Mechanisms of resistance to rapamycin analogs in renal cell carcinoma remain unclear and study results suggest that PBRM1 loss may contribute to sensitivity through complex transcriptional effects.

6. Low PBRM1 expression is associated with early stages of clear cell renal cell carcinoma.

7. Study suggests that reduced expression of PBRM1 and VHL in clear cell renal cell carcinoma is correlated with an increased tumor aggressiveness.

8. These findings indicate that PBRM1 mutation (and resultant loss of expression) is a late event during biliary carcinogenesis

9. Clear-cell renal carcinoma cell lines whose ability to proliferate in vitro and in vivo is sensitive to wild-type BAF180, but not a tumor-associated BAF180 mutant, showed that the growth suppression by BAF180 is linked to its ability to form a canonical PBAF complex containing BRG1 that dampens the HIF transcriptional signature.

10. Knockdown of PBRM1 in colon cancer cells increased the expression of two receptor genes (RIG-I and MDA5) and upregulated interferon (IFN)-related and inflammation-related gene signatures. Lower PBRM1 expression was associated with advanced pathological grade and poorer survival of colorectal cancer (CRC) patients, indicating that PBRM1 could serve as a potential prognostic biomarker for CRC.

11. kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers.

12. PBRM1 mutation is associated with small Cell Lung Cancer.

13. These findings indicate that PBRM1 alters cell cycle progression and inhibits proliferation and migration of renal cell carcinoma ACHN cells through the chemokine/chemokine receptor pathway.

14. our integrative analysis suggested that methylation and miRNA alterations were likely the downstream events associated with PBRM1 truncation mutations. In summary, this study provided some important insights into the understanding of tumorigenesis driven by PBRM1 truncated mutations in Clear cell renal cell carcinoma (ccRCC). The approach may be applied to many driver genes in various cancers.

15. BAP1 and PBRM1 loss is seen frequently in intrahepatic cholangiocarcinoma

16. PBRM1 gene deletion is associated with chordoma.

17. conclude that four of the BDs act together to target PBRM1 to sites on chromatin; when a single BD is mutated, PBRM1 no longer controls gene expression properly, leading to increased cell proliferation

18. Synthetic lethality screening identifies TIP60-dependent radiation sensitivity in the absence of BAF180.

19. Functionally, suppression of PBRM1 expression promoted cell proliferation and cell cycle progression

20. PBRM1 re-expression led to upregulation of genes involved in cellular adhesion, carbohydrate metabolism, apoptotic process and response to hypoxia, and a downregulation of genes involved in different stages of cell division.

Mouse (Murine) Polybromo 1 (PBRM1) interaction partners

1. Data show that 100% of von Hippel-Lindau tumor suppressor protein (Vhl) / polybromo 1 protein (Pbrm1) knockout mice developed renal cancers by 20 months of age.

2. We conditionally targeted Bap1 and Pbrm1 (with Vhl) in the mouse using several Cre drivers.Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of Clear cell renal cell carcinoma (ccRCC)origins

3. dual inactivation of Vhl with either Bap1 or Pbrm1 results in faithful genetically engineered murine models of clear cell renal cell carcinoma (ccRCC).

4. Data suggest BAF180 protein as a critical regulator of cellular senescence and HSC homeostasis, which is at least partially regulated through BAF180-mediated suppression of cell cycle regulator p21 expression.

5. kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers.

6. Data demonstrate a function for BAF180 in promoting genome stability that is distinct from its well-characterized role in transcriptional regulation.

7. BAF180 is a repressor of IL-10 transcription in Th2 cells and suggest that the differential recruitment of different SWI/SNF subtypes can have direct consequences on chromatin structure and gene transcription.

8. BAF180 is critical for coronary vessel formation.