Menin controls the concentration of retinoblastoma protein

Abstract

Menin, the protein encoded by the Multiple Endocrine Neoplasia type 1 gene, is involved in the cell cycle control through its participation in functional dynamics of chromatin and regulation of transcription. RB, the protein of the retinoblastoma gene RB1, controls the progression of the cell cycle and is regulated in its activity by means of a feedback by phosphorylation. Studies in double heterozygous knockout mice for Men1 and the Retinoblastoma gene Rb1 have recently indicated that both genes may be implicated in the same pathways. In the course of our studies on Menin, we found that after suppression or in absence of Menin, RB1 expression was strongly reduced in a posttranscriptional manner. Under conditions of growth arrest, the hyperphosphorylated form of RB was most strongly affected, whereas its hypophosphorylated form was less or not at all reduced. Our findings confirm the hypothesis that the pathways of two tumor suppressor genes are connected.

MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response

“…Men1 f/f p = 0.0005 p = 0.005 p = 0.0298 p = 0.0029 2.5 report that menin positively regulates Rb activity in a posttranscriptional manner 24 . Altogether, our data demonstrate that menin is a pivotal regulator for p53/Rb pathways.…”

Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma

“…This could explain how menin may recognize certain sequences in p27 Kip1 , p18 Ink4c and cyclin B2 genes thereby recruiting MLL and HDAC to their respective locations. Furthermore, Ivo et al (2011) reported that menin increases the cellular concentration of RB protein via unknown mechanisms. Taken together, the RB pathway is likely a direct downstream target of menin signaling.…”

Multiple Endocrine Neoplasia Type 1

“…347 Indeed, paseriotide, which is a long-acting somastostatin analogue, has been reported to have antisecretory, antiproliferative, and proapoptotic activity when used to treat insulinomas that developed a mouse model for MEN 1. [358][359][360] Indeed, menin has been shown to control the concentration of RB, 359 and loss of the retinoblastoma binding protein 2 (RBP2) histone deinethylase has been reported to suppress tumorigenesis in mice deleted for Men1. 356 This demonstrates previously unknown roles for menin in the development of multiple tissues, which may include regulating the expression of extracellular matrix proteins that are required during organogenesis.…”