CEP57L1

CEP57L1 is a centriolar protein that cooperates with CEP57 to maintain mother–daughter centriole engagement during interphase; co-depletion of both proteins causes precocious centriole disengagement, centriole reduplication, and chromosome segregation errors without altering cell-cycle progression (PMID:33492359). Disengaged daughter centrioles resulting from CEP57/CEP57L1 loss convert into centrosomes in a Plk1-dependent manner, placing CEP57L1 upstream of Plk1-driven centrosome maturation (PMID:33492359). CEP57L1 protein levels are controlled by ubiquitin-mediated proteasomal degradation through a KLF5–KLHL13–CUL3 axis; impairment of this pathway leads to CEP57L1 accumulation, centrosome amplification, and enhanced cancer cell migration and metastasis (PMID:41443421).

1. 2021 High

   Resolving whether individual centriole-engagement factors are sufficient or redundant, this study established that CEP57 and CEP57L1 cooperatively maintain centriole engagement during interphase, with their combined loss—but not single depletion—causing premature disengagement, reduplication, and segregation errors.

   Evidence siRNA co-depletion in human cells with centriole counting, engagement assays, and chromosome missegregation readouts

   PMID:33492359

   Open questions at the time

   • The structural basis of CEP57L1 tethering at the centriole linker is unknown
   • Whether CEP57 and CEP57L1 form a direct complex or act independently at the same site is unresolved
   • Relative contributions of each paralog across different cell types have not been quantified
2. 2021 High

   Addressing how disengaged daughter centrioles acquire centrosome identity, epistasis experiments showed that the centrosome conversion following CEP57/CEP57L1 co-depletion depends on Plk1 activity, placing CEP57L1 function upstream of Plk1-mediated centrosome maturation.

   Evidence Plk1 inhibition in CEP57/CEP57L1 co-depleted human cells with centrosome conversion readout

   PMID:33492359

   Open questions at the time

   • Direct biochemical interaction between CEP57L1 and Plk1 has not been tested
   • Whether Plk1 is recruited to the disengaged daughter or the mother centriole is unclear
3. 2025 Medium

   Addressing how CEP57L1 abundance is controlled, this study identified a KLF5–KLHL13–CUL3 ubiquitin ligase axis that targets CEP57L1 for proteasomal degradation, linking its accumulation to centrosome amplification and metastatic behavior in cancer cells.

   Evidence KLF5/KLHL13/CUL3 knockdown and overexpression, western blotting for ubiquitination, AGE treatment in vitro, and mouse metastasis model

   PMID:41443421

   Open questions at the time

   • Direct ubiquitination of CEP57L1 by the KLHL13–CUL3 complex has not been reconstituted in vitro
   • The specific ubiquitin chain type and degron on CEP57L1 are uncharacterized
   • Whether this degradation pathway operates in non-cancer cells or during normal cell-cycle control is unknown

• It remains unknown how CEP57L1 is physically anchored at the centriole engagement site, whether it directly contacts PCM or linker components, and whether its role in centriole engagement is conserved across vertebrates.
• No structural model of CEP57L1 at the centriole exists
• No interactome or proximity-labeling data have been reported for CEP57L1
• Physiological consequences of CEP57L1 loss in animal models are unexplored