Fig 1.
CP represents a multifunctional cancer-associated hub protein and P1, P2, P3, P4 & P5 are its direct interactors (First Hop Protein Interactors or FHPIs of CP).
P1-1, P1-2 & P1-3 are the interactors of P1 (Second Hop Protein Interactors or SHPIs of CP), P2-1, P2-2 & P2-3 are the interactors of P2 and so on. Red-borders have been used to mark the oncoproteins. Sequence analysis (using MEME for de-novo motif identification) of all the interactors of a particular FHPI (e.g CP, P1-1, P1-2, and P1-3 for P1) may reveal some shared sequence patterns (e.g. m1 & m2 among interactors of P1, m1, m2, m3 & m4 among interactors of P2 etc). Alignment of the peptide sequences from CP corresponding to all such motifs (p1 from m1, p2 from m2 etc) may then identify a common peptide (OLP) from the overlapping sequence positions. This OLP may play a key role in mediating interactions with multiple FHPIs and therefore help in designing orthosteric inhibitors that can be targeted to block any of the CP-FHPI interactions by making it specific to the binding site of CP on a particular FHPI (e.g. P1).
Fig 2.
(A) Eight OLP sequences (each marked by a different background colour) were identified by Multiple Sequence Alignment of the peptide sequences in MYC corresponding to all significant motifs (E-value<1.0) inferred by MEME from its SHPI network. (B) Diagrammatic representation of an OLP sequence 114SFICDPDD121 (marked with orange background) identified in MYC, which may interact with five FHPIs. The nodes representing oncoproteins have been marked with a red border.
Table 1.
Overlapping Linear Motifs (OLPs) found in the cancer-associated hub proteins (CPs) MYC, APC and MDM2.