Identifying players in the functional network around pRB

The pro-death role of Cited2 in stroke is regulated by E2F1/4 transcription factors

“…Although E2F1 is likely one mediator of Cited2 expression, the role of E2F members in general is more complex. This is exemplified by (a) our observation that E2F1 levels can remain high, whereas Cited2 levels gradually decrease during hypoxia; and (b) an increasingly defined role of E2F members as part of active repressor complexes (32,33). Our own present data suggest that some E2F regulatory sites when mutated, at least in a murine context, may actually lead to increase in Cited2 relevant promoter activity.…”

“…For example, it appears that E2F1-3 act as transcriptional activators and interact with Rb, whereas E2F4 and E2F5 preferentially bind to p130/p107 to mediate repression of transcription (31). How repression is regulated is not completely clear, although a novel E2F4-containing repressive complex (DREAM complex) has been recently described (32,33). Whether this complex is relevant in neuronal injury is unclear.…”

Targeting RB1 Loss in Cancers

“…LATS2 is primarily a component of Hippo pathway, but appeared to phosphorylate dual-specificity tyrosinephosphorylation-regulated kinase 1A (DYRK1A), which then phosphorylates LIN52 a subunit of DREAM (DP-1, RB1, E2Fs and MuvB) complex. Therefore, loss of LATS2 impairs functions of DREAM complex, cooperating with RB1 loss to promote tumor development [104]. In this scenario, in sharp contrast to SUCLA2, loss of LATS2 generates certain growth advantages to RB1-deficient cancer.…”

“…Cancers 2021, 13, x 10 of 15 pairs functions of DREAM complex, cooperating with RB1 loss to promote tumor development [104]. In this scenario, in sharp contrast to SUCLA2, loss of LATS2 generates certain growth advantages to RB1-deficient cancer.…”