CIB1: A small protein with big ambitions

Abstract

Calcium-and integrin-binding protein 1 (CIB1) is a small, ubiquitously expressed protein that was first identifiedas anintracellularbindingpartner of aplatelet-specifica-integrin cytoplasmic tail.Although early studies revealed a role for CIB1 in regulating platelet integrin activity, recent studies have indicated amore diverse role for CIB1 in many different cell types and processes, including calcium signaling, migration, adhesion, proliferation, and survival. Increasing evidence also points to a novel role for CIB1 in cancer and cardiovascular disease. In addition, an array of CIB1 binding partners has been identified that provide important insight into how CIB1may regulate these processes. Some of these binding partners include the serine/threonine kinases, p21-activated kinase 1 (PAK1), apoptosis signal-regulating kinase 1 (ASK1), and polo-like kinase 3 (PLK3). Structural and mutational studies indicate thatCIB1 bindsmost or all of its partners via awell-definedhydrophobic cleft. Although CIB1 itself lacks known enzymatic activity, it supports the PI3K/AKTandMEK/ERKoncogenic signaling pathways, in part, by directly modulating enzymes in these pathways. In this review, we discuss our current understanding of CIB1 and key questions regarding structure and function and how this seemingly diminutive protein impacts important signaling pathways and cellular processes in human health and disease.-Leisner,T.M.,Freeman, T. C.,Black, J.L., Parise, L. V. CIB1: A small protein with big ambitions.