Disease relevance of PLEKHO1

• To elucidate the functions of CKIP-1, we generated human osteosarcoma cell lines with tetracycline-regulated expression of Flag-CKIP-1 [1].
• Here, we report that overexpression of CKIP-1 in SK-BR-3 breast cancer cells prevents p53 degradation induced by cycloheximide treatment through increase of p53 N-terminal Ser-15 phosphorylation level [2].

High impact information on PLEKHO1

• C-terminal fragments of cleaved CKIP-1 strongly repress AP-1 activity [3].
• Role for the pleckstrin homology domain-containing protein CKIP-1 in AP-1 regulation and apoptosis [3].
• RNA interference of CKIP-1 or overexpression of c-Jun attenuates the sensitivity to apoptosis, indicating a novel role of CKIP-1 in apoptosis [3].
• Overall, our results are consistent with CKIP-1 playing a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein [1].
• To elucidate the mechanisms behind the observed phenotype, we utilized tandem affinity purification to isolate CKIP-1 interacting proteins [1].

Biological context of PLEKHO1

• During apoptosis, CKIP-1 is cleaved by caspase-3 and translocated to the cytoplasm and then to the nucleus [3].
• Importantly, similar to Nmi and contrast to IFP35, CKIP-1 inhibits tumor cell growth and Akt-mediated cell survival [4].
• Collectively, our data supports a model whereby CKIP-1 is a non-enzymatic regulator of CK2alpha that regulates the cellular functions of CK2alpha by targeting or anchoring CK2alpha to specific cellular localization or by functioning as an adapter to integrate CK2alpha-mediated signaling events with components of other signal transduction pathways [5].

Anatomical context of PLEKHO1

• Finally, we demonstrate that CKIP-1 and CK2 inhibit the activity of actin capping protein at the barbed ends of actin filaments [1].
• These studies demonstrated that CKIP-1 can recruit CK2 to the plasma membrane [6].

Physical interactions of PLEKHO1

• Interestingly, CKIP-1 is localized both at the plasma membrane and in the nucleus dependent on the cell types, and only the plasma membrane-localized CKIP-1 could form a complex with ATM [2].
• The PH domain containing protein CKIP-1 binds to IFP35 and Nmi and is involved in cytokine signaling [4].

Other interactions of PLEKHO1

• Importantly, CKIP-1 recruits nuclear ATM proteins partially to the plasma membrane [2].
• CKIP-1 (casein kinase-2 interacting protein-1) is implicated in muscle differentiation, regulation of cell morphology and actin cytoskeleton [2].
• In this study, we present evidence from deletion analysis of CKIP-1 suggesting that a C-terminal region containing a putative leucine zipper has a role in regulating its nuclear localization [5].

References