Pleckstrin homology domain-interacting protein (PHIP)

Pleckstrin homology domain-interacting protein (PHIP; also known as RepID, DCAF14, WDR11, among other aliases) is a WD repeat-containing protein that functions as a chromatin-associated substrate receptor (DCAF) within the Cullin 4-RING E3 ubiquitin ligase (CRL4) complex[3][4]. PHIP/RepID recruits and localizes the CRL4 complex to replication origins in interphase, thereby facilitating the ubiquitination and timely degradation of key cell cycle and DNA replication regulators[3]. In mitosis, CRL4 detaches from RepID and instead engages other DCAFs to regulate transitions such as the metaphase-to-anaphase switch by targeting spindle checkpoint proteins (e.g., BUB3)[3]. PHIP has been implicated in cancer and cell proliferation disorders as a regulatory node in chromatin remodeling, cell cycle control, and protein turnover[1][3]. Loss or mutation of PHIP, or interference with CRL4-RepID complex formation, disrupts cell cycle progression and can impact sensitivity to chemotherapeutic agents like paclitaxel[3].

Other names

PH-interacting proteinDCAF14WDR11ndrpBRWD2RepIDFLJ20705DDB1- and CUL4-associated factor 14IRS-1 PH domain-binding proteinWD repeat-containing protein 11DDB1 and CUL4 associated factor 14CHUJANSDIDODpleckstrin homology domain interacting protein

Chaperoning recruitment and assembly of the CRL4 (Cullin 4-RING ligase) E3 complex to replication origins and chromatin Enabling ubiquitination and degradation of cell cycle regulators and mitotic checkpoint proteins (e.g., BUB3)[3]