A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability

  title={A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability},
  author={Joseph T. Woitach and Minghuang Zhang and C. H. Niu and Snorri Thorgeirsson},
  journal={Nature Genetics},
The retinoblastoma (RB) gene is one of the most extensively studied tumour-suppressor genes. Deletion or inactivation of both RB alleles is an essential, rate-limiting step in the formation of retinoblastoma and osteosarcoma that arise in families that carry mutant RB (ref. 2). RB inactivation is also found in other human tumours. Whereas loss of RB function is associated with the loss of cellular proliferative control, introduction of a wild-type RB can suppress cell growth and tumorigenicity… 

Retinoblastoma protein partners.

Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas

The results demonstrate the importance of ubiquitin–proteasome pathway in the regulation of cell growth and oncogenic transformation, and indicate that gankyrin overexpression contributes to hepatocarcinogenesis by destabilizing RB1.

Novel retinoblastoma binding protein RBBP9 modulates sex-specific radiation responses in vivo.

This work studied the effects of acute and chronic low dose radiation exposure on the induction of RBBP9 and RB signaling pathway in vivo in mouse spleen and found that R BBP9 played a pivotal role in IR responses in vivo.

Structure-function analysis of the retinoblastoma tumor suppressor protein – is the whole a sum of its parts?

This review will focus on literature that investigates pRB by isolating functions based on binding sites within the pocket domain and the prospects for using this approach to further explore the unknown functions of pRB.

Differential Roles for the Retinoblastoma Protein in Cycling and Quiescent Neural Populations

It is reported that Rb regulates the expression of neogenin, a gene encoding a receptor involved in cell migration and axon guidance, and it is demonstrated that regulation of neogensin expression is required for neural precursor migration.

Role of LXCXE motif-dependent interactions in the activity of the retinoblastoma protein

It is suggested that LXCXE-dependent interactions are not essential for pRb to exert growth arrest, and directly targeting HDAC2 to E2F responsive promoters as an E 2F/HDAC hybrid protein failed to effect cell cycle arrest.

Human retinoblastoma binding protein 9, a serine hydrolase implicated in pancreatic cancers.

Structural- function studies of RBBP9 suggest possible routes for novel cancer drug discovery programs and sequence analysis suggests that R BBP9 belongs to the α/β hydrolase superfamily of enzymes.

RBBP9: A tumor-associated serine hydrolase activity required for pancreatic neoplasia

Retinoblastoma-binding protein 9 (RBBP9) is identified as a tumor-associated serine hydrolase that displays elevated activity in pancreatic carcinomas, and a previously uncharacterized serineHydrolase activity associated with epithelial neoplasia is defined, demonstrating the potential benefit of functional proteomics in the identification of new therapeutic targets.

Assignment1 of the Bog gene (RBBP9) to syntenic regions of mouse chromosome 2G1–H1 and human chromosome 20p11.2 by fluorescence in situ hybridization

A rat cDNA encoding a novel protein called Bog is isolated from a rat liver epithelial cell line and the Bog gene was mapped to mouse chromosome 2G1–H1 and to human chromosome 20p11.2 to gain insight into the possible relationship with the transformed phenotype in other cell types.



The retinoblastoma gene functions as a growth and tumor suppressor in human bladder carcinoma cells.

The concept that the RB gene acts as both a growth and tumor suppressor in bladder cancer cells is supported, using an RB expression plasmid transfected into the bladder carcinoma cell line HTB9.

Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene.

It is suggested that RB inactivation can play a significant role in the genesis of a common adult neoplasm and that restoration of normal RB-encoded protein in tumors could have clinical utility.

Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells.

Analysis of polyclonal anti-synthetic peptide serum indicates that inactivation of the RB protein, p105-Rb, is universal in retinoblastoma cells, vindicating the predictions of the Knudson "two-hit" hypothesis.

Inactivation of the retinoblastoma susceptibility gene in human breast cancers.

The retinoblastoma susceptibility gene is shown to be inactivated in two of nine human breast cancer cell lines examined, significant in relation to proposed genetic mechanisms of breast cancer formation.

Retinoblastoma gene deletions in human glioblastomas.

Examination of a group of benign and malignant gliomas for evidence of structural alterations of the retinoblastoma susceptibility gene suggests that RB gene abnormalities may contribute to the development of glioblastomas.

Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells.

This demonstration of suppression of the neoplastic phenotype by a single gene provides direct evidence for an essential role of the RB gene in tumorigenesis.

Altered expression of the retinoblastoma (RB) gene in small-cell carcinoma of the lung.

The results strongly suggest that inactivation of the RB gene might be involved in the development of lung cancers, especially of SCCs.

Identification of a growth suppression domain within the retinoblastoma gene product.

When full-length RB and certain truncated forms were synthesized in human RB -/- cells, it was found that the minimal region necessary for overt growth suppression extended from residue 379 to 928, and a functional pocket domain and sequences extending from the carboxy-terminal boundary of the pocket to theCarboxyl terminus of the protein were both necessary for growth suppression.