Emerging roles of RB family: New defense mechanisms against tumor progression

Abstract

The retinoblastoma (RB) family of proteins, including RB1/p105, retinoblastoma-like 1 (RBL1/p107), and retinoblastoma-like 2 (RBL2/p130), is principally known for its central role on cell cycle regulation. The inactivation of RB proteins confers a growth advantage and underlies multiple types of tumors. Recently, it has been shown that RB proteins have other important roles, such as preservation of chromosomal stability, induction and maintenance of senescence and regulation of apoptosis, cellular differentiation, and angiogenesis. RB proteins are involved in many cellular pathways and act as transcriptional regulators able to bind several transcription factors, thus antagonizing or potentiating their functions. Furthermore, RB proteins might control the expression of specific target genes by recruiting chromatin remodeling enzymes. Although many efforts have been made to dissect the different functions of RB proteins, it remains still unclear which are necessary for cancer suppression and the role they play at distinct steps of carcinogenesis. Moreover, RB proteins can behave differently in various cell types or cell states. Elucidating the intricate RB protein network in regulating cell fate might provide the knowledge necessary to explain their potent tumor suppressor activity and to design novel therapeutic strategies.

Molecular Pathways: Harnessing E2F1 Regulation for Prosenescence Therapy in p53-Defective Cancer Cells

“…26). RB protein family proteins, RB (p105), p107, and p130, have overlapping functions in cell-cycle control (26) and have compensatory and complementary roles in senescence regulation (27,28). For example, in the absence of functional RB, p107 was shown to primarily mediate irradiationinduced senescence in prostate cancer cells (29).…”

Association of Aberrant Methylation at Promoter Regions of Tumor Suppressor Genes with Placental Pathologies

“…Silencing of tumor suppressor genes mediated by DNA methylation is a hallmark of human cancer [14]. Lower expression/loss of function due to epigenetic inactivation via aberrant methylation has been reported for RASSF1A [8,15], APC [16], RB1 [11,17], P16 [9] and PRKCDBP [18][19][20], as an important factor for development of various cancers.…”

“…These tumor suppressor genes are involved in regulating cellular differentiation, senescence, apoptosis, cell cycle arrest, DNA repair, microtubule dynamics and genomic instability [8][9][10][11][12][13]. Silencing of tumor suppressor genes mediated by DNA methylation is a hallmark of human cancer [14].…”

Molecular Determinants for the Inactivation of the Retinoblastoma Tumor Suppressor by the Viral Cyclin-dependent Kinase UL97

“…Rb is the master regulator of a pathway that controls cell cycle progression and that is aberrant in most human tumors (2). Additional pathways regulated by Rb and relevant to cancer include those controlling genome stability, senescence, apoptosis, differentiation, angiogenesis, and glutamine metabolism (3)(4)(5)(6)(7). Rb family members p107 and p130 serve similar functions and are regulated in an analogous manner.…”