These promoter regions are known to be bound by the E2F family proteins (E2F-1 to E2F-8) and retinoblastoma (RB) family proteins (RB1, p107, and p130), among which E2F-4 and p130 were strongly up-regulated in HSP27-knockdown cells.
We report that RB-depleted maturing (ARR3<sup>+</sup>) but not immature (ARR3<sup>-</sup>) human cone precursors enter the cell cycle, proliferate, and form retinoblastoma-like lesions with Flexner-Wintersteiner rosettes, then form low or nonproliferative premalignant retinoma-like lesions with fleurettes and p16<sup>INK4A</sup> and p130 expression, and finally form highly proliferative retinoblastoma-like masses.
While mutations in the retinoblastoma (RB1) tumor suppressor have been reported in lung cancer, mainly in small cell lung carcinoma, the tumor suppressive role of its relatives p107 and p130 is still a matter of debate.
Moreover, while forced RB or p130 expression repressed the activity of a luciferase reporter driven by the MYB-E2F element, co-expression of MAZ proteins not only reverted repression, but also activated transcription.
Several murine retinoblastoma models have been generated by deleting the genes encoding for retinoblastoma susceptibility protein pRb and one of its family members p107 or p130.
Further investigation into the mechanisms of MAGE-A11 function in prostate cancer demonstrated interactions with the retinoblastoma-related protein p107 and Rb tumor suppressor but no interaction with p130 of the Rb family.
A combined deletion of the RB proteins, RB, p107 and p130 (triple-mutant; TM), prevents SATB1-induced G1 arrest, which is restored upon the reintroduction of RB into SATB1-expressing TM fibroblasts.
To investigate the functional relevance of this observation, we inactivated the RB pathway in the liver of adult mice by deleting the three members of the Rb (Rb1) gene family: Rb, p107, and p130.
Although the association of retinoblastoma and Peters anomaly in this patient may be coincidental, it raises the question of whether the RBL2 mutation contributed to both conditions.
We now demonstrate that loss of both RB1 tumor suppressor gene alleles initiates quiescent RB1(-/-) retinomas with low level genomic instability and high expression of the senescence-associated proteins p16(INK4a) and p130.
Mutations disrupting the normal nuclear localization signal of the retinoblastoma-related gene Rb2/p130 have been documented in BL cell lines and primary tumors from endemic areas.
In this study, we focused on the retinoblastoma-related protein p130 in AD. p130 is a transcriptional regulator that complexes with E2F4/5 in the nucleus and suppresses genes that regulate entry into the cell cycle.
Animals lacking Rb and/or its family members p107 and p130 have led scientists to uncover new and exciting roles for this protein family in development as well as tumor suppression.
The best-known cellular targets of the HPV-16 E7 oncoprotein are the retinoblastoma tumor suppressor protein pRB and the related pocket proteins p107 and p130.
We have recently reported that loss of expression of the retinoblastoma-related protein pRb2/p130 correlates with low apoptotic index, suggesting that RB2/p130 gene could be involved in retinoblastoma.
We recently reported that loss or lowering of pRb2/p130 expression is mainly due to aberrant Rb2/p130 promoter methylation, in retinoblastoma tumors, and indicated that epigenetic silencing of Rb2/p130 can impair its function to negatively regulate cell cycle progression as well as apoptotic response.
The human cytomegalovirus pp71 protein employs an LXCXD motif to attack the retinoblastoma family members and induce DNA synthesis in quiescent cells. pp71 binds to and induces the degradation of the hypophosphorylated forms of the retinoblastoma protein and its family members p107 and p130 in a proteasome-dependent manner.