Bin1 functionally interacts with Myc and inhibits cell proliferation via multiple mechanisms

Mechanisms of apoptosis by c-Myc

“…A good candidate, however, has emerged in the ATM-related protein TRRAP, an NTD-binding protein that is part of the SAGA complex which includes histone deacetylases implicated in activation events (Grant et al, 1998;McMahon et al, 1998;Saleh et al, 1998). The activation activity of the NTD may also be influenced by interactions with the retinoblastoma (Rb)-related protein p107 (Beijersbergen et al, 1994;Gu et al, 1994;Hoang et al, 1995), whose binding to c-Myc may be modulated by cyclin D/CDK4 phosphorylation (Hass et al, 1997), or with the adaptor protein and tumor suppressor Bin1 (Sakamuro et al, 1996;Elliott et al, 1999). The NTD is also reported to interact with a-tubulin (Alexandrova et al, 1995), PAM, a large protein which includes RCC1-like repeats suggesting a role in chromatin regulation , MM-1, a nucleocytoplasmic adaptor protein that inhibits transactivation by c-Myc, and AMY-1, a small protein reported to potentiate the transactivation activity of cMyc (Taira et al, 1998).…”

“…Bin1 was initially identi®ed in a screen for MB1-binding proteins but its interaction with c-Myc requires both of the conserved Myc boxes (Sakamuro et al, 1996). Bin1 inhibits the oncogenic and transcriptional transactivation properties of c-Myc in a binding domain-dependent manner (Elliott et al, 1999;Sakamuro et al, 1996). Bin1 will also inhibit the oncogenic properties of adenovirus E1A, papilloma virus E7, and mutant p53, through domains that are dispensable for e ects on c-Myc (Elliott et al, 1999).…”

“…Bin1 inhibits the oncogenic and transcriptional transactivation properties of c-Myc in a binding domain-dependent manner (Elliott et al, 1999;Sakamuro et al, 1996). Bin1 will also inhibit the oncogenic properties of adenovirus E1A, papilloma virus E7, and mutant p53, through domains that are dispensable for e ects on c-Myc (Elliott et al, 1999). Investigations of the status of the Bin1 gene (WechslerReya et al, 1997b) in tumor cells supports the hypothesis that Bin1 is a tumor suppressor with important growth regulatory roles (Sakamuro et al, 1996;Wechsler-Reya et al, 1997b;Elliott et al, 1999;Mao et al, 1999; J DuHadaway, K Ge and GC Prendergast, manuscripts submitted).…”

“…First, the nuclear tyrosine kinase c-Abl was shown recently to interact with but not phosphorylate Bin1 in vivo (Kadlec and Pendergast, 1997). c-Abl binding is mediated by the SH3 domain of Bin1 (Kadlec and Pendergast, 1997), which is dispensable for its association with c-Myc (Sakamuro et al, 1996;Elliott et al, 1999). A fraction of c-Abl in cells is reported to be activated at focal adhesions where integrins are located (Lewis et al, 1996;Taagepera et al, 1998), so since apoptosis by c-Myc is in¯uenced by integrin signals (Crouch et al, 1996) there may be links via this route to c-Abl activation.…”

“…an SH3 domain). Bin1 may be linked to transcriptional programs, though, since it can inhibit the transactivation properties of c-Myc (Elliott et al, 1999).…”