Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product

Rustgi, Anil K.; Dyson, Nicholas J.; Bernards, René

doi:10.1038/352541a0

Cited by 294 publications

(100 citation statements)

References 26 publications

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“…The regulation of cell cycle progression by pRb can also be disrupted by loss of control of cyclin: CDK-complexes by either p16 or p21 families of cyclin-CDKinhibitors, such as the loss of p27 expression shown in the present study. Furthermore, while the G 1 /S regulation by pRb is mediated by binding to E2F family of transcription factors, later in the cell cycle pRb can be bound by oncoproteins like c-Myc, c-Abl, and MDM2 (Rustgi et al, 1991;Welch and Wang, 1993;Xiao et al, 1995). Considering all these mechanisms in the pRb pathway, our finding of the apparently paradoxical correlation between pRb expression and cell proliferation (Ki-67 expression) seems only rational.…”

Section: Discussionmentioning

confidence: 73%

Cell cycle regulators p27 and pRb in lymphomas – correlation with histology and proliferative activity

Sauroja

Rajamäki

Punnonen³

et al. 2000

Br J Cancer

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The non-Hodgkin's lymphomas (NHL) are a heterogeneous group of malignancies arising from B-or T-cell lymphatic systems. The current REAL classification of lymphomas is based on histology, immunohistochemistry and genetic changes (Harris et al 1994). Several regulators of the cell cycle are currently well known and their function and expression has been shown to be important in the initiation of cancer (Graña and Reddy, 1995;Hirama and Koeffler, 1995;Sherr, 1996). Because of their importance in the regulation of the cell cycle the presence and function of these regulator proteins in specific malignancies needs to be further studied.The cell cycle is regulated by cyclins, cyclin-dependent kinases (CDK) and cyclin-CDK complex inhibitors. These inhibitory proteins can be divided into two classes differing in both sequence homology and their targets of inhibition (Hall et al, 1995). The CIP (cyclin inhibitory protein)/KIP(kinase inhibitory protein) gene family products (p21, p27 and p57) bind to cyclins, whereas INK4 gene family products (p15, p16, p18 and p19) bind to CDK4/6 (Graña and Reddy, 1995;Hall et al, 1995;Hirama and Koeffler, 1995;Sherr and Roberts, 1995;Sherr, 1996). Cyclin D and CDK form complexes able to phosphorylate pRb protein which functions in its hypophosphorylated form as a negative regulator of the cell cycle during G 1 phase. Cyclin D:CDK4/6 complexes phosphorylate retinoblastoma (RB) protein which then releases transcription factors, and allows cells to enter the S phase. Mutations of the RB gene or alterations in cyclin D:CDK complex inhibitory genes lead to loss of the principal function of the Rb productgrowth control at G 1 /S border.The expression of cyclin-dependent kinase inhibitor p27/Kip1, a member of the p21 family, is high in cells inhibited by cell contact, by the cytokine transforming growth factor-β (TGF-β), or by serum deprivation (Polyak et al, 1994). The present evidence indicates that TGF-β induces cell cycle arrest through the cooperative action of p15 and p27, or p21 (Reynisdóttir et al, 1995).The non-Hodgkin's lymphoma is a common malignancy, and its incidence is increasing in older populations (Zheng et al, 1992). Although NHL can be very invasive, treatments should not be started until the NHL has been classified according to, e.g. the REAL classification, since treatments vary considerably between the subgroups. The classification of lymphomas is difficult and the aggressiveness is variable within the same diagnosis. Therefore, specific markers are needed to evaluate the aggressiveness of the tumour and to improve the accuracy of classification. We have studied proliferation status and the expression of p27 and pRb, which are both cell cycle regulators involved in cyclin D-mediated responses, by immunohistochemical staining in non-Hodgkin's lymphomas. PATIENTS AND METHODSThe patient population included 96 non-Hodgkin's lymphoma (NHL) patients (age 16-90 years), who were treated at the Turku University Central Hospital for various histological subtypes of B-cell non-Hodg...

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Section: Discussionmentioning

confidence: 73%

Cell cycle regulators p27 and pRb in lymphomas – correlation with histology and proliferative activity

Sauroja

Rajamäki

Punnonen³

et al. 2000

Br J Cancer

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“…First, c-myc has been shown to interact with the retinoblastoma protein, pRb, in some experiments. Cmyc directly interacts with speci®c domains on pRb in vitro and alters transcription of target genes (Hateboer et al, 1993;Maheswaran et al, 1991;Rustgi et al, 1991). Furthermore, pRb directly binds the UBF component of the PolI activation apparatus and inhibits PolI transcription in vitro (Cavanaugh et al, 1995;Voit et al, 1997).…”

Section: C-myc Target Genes and Growth Controlmentioning

confidence: 99%

The role of c-myc in cellular growth control

1999

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“…MAP kinase [previously designated epidermal growth factor receptor threonine (ERT) kinase] has also been shown to phosphorylate Myc on Ser-62 both in vitro and in vivo Seth et al, 1991;Pelech & Sanghera, 1992). No function has as yet been given to this site, but since it lies within a region which is required for transcriptional activation (Lech et al, 1988; and for the proposed association with the product of the retinoblastoma susceptibility gene (Rustgi et al, 1991), its phosphorylation could regulate these associations. element (MRE; Biedenkapp et al, 1988).…”

Section: Nf-kbmentioning

confidence: 99%

“…At least seven cellular proteins can complex with pRB in vitro (Kaelin etal., 1991;Huang etal., 1991), including the transcription factors c-Myc (Rustgi et al, 1991) and E2F (Bandara & La Thangue, 1991;Chellappan et al, 1991;Bagchi et al, 1991;Chittenden et al, 1991). pRB is therefore thought to act as a transcriptional repressor by sequestering key proteins which are required for cell cycle progression (Wagner & Green, 1991).…”

Section: Prbmentioning

confidence: 99%