CUL4B
Description
The CUL4B (cullin 4B) is a protein-coding gene located on chromosome X.
Cullin-4B is a protein encoded by the CUL4B gene located on the X chromosome. It shares significant sequence similarity with CUL4A, with which it participates in certain E3 ubiquitin ligase functions. CUL4B is primarily expressed in the nucleus and regulates essential processes, including cell cycle progression, chromatin remodeling, and neurological and placental development in mice. In humans, CUL4B is linked to X-linked intellectual disability and frequently exhibits mutations in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses like HIV can utilize CUL4B-based complexes to facilitate viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide. CUL4B consists of 913 amino acids and shares a high degree of sequence identity (84%) with CUL4A, except for its unique N-terminal region. The N-terminus of CUL4B is disordered, and its structural and functional properties remain unclear. CUL4B binds to the beta-propeller of the DDB1 adaptor protein, which interacts with numerous DDB1-CUL4-Associated Factors (DCAFs). This interaction is crucial for recruiting substrates to the ubiquitin ligase complex.
CUL4B is a core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes, which are responsible for ubiquitination and subsequent proteasomal degradation of target proteins. The specific function of the E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition subunit. CUL4B acts as a scaffold protein within the complex, contributing to catalysis by positioning the substrate and the ubiquitin-conjugating enzyme. CUL4B participates in polyubiquitination of CDT1, histone H2A, histone H3, and histone H4 in response to radiation-induced DNA damage. CUL4B is targeted to UV-damaged chromatin by DDB2 and plays a role in DNA repair and DNA replication. Several DCX complexes, containing either TRPC4AP or DCAF12 as substrate-recognition components, are part of the DesCEND (destruction via C-end degrons) pathway. This pathway recognizes a C-degron located at the extreme C-terminus of target proteins, leading to their ubiquitination and degradation. The DCX(AMBRA1) complex is a master regulator of the transition from the G1 to the S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2, and CCND3). The DCX(AMBRA1) complex also regulates Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of the Elongin-C (ELOC) component of CRL5 complexes. CUL4B is necessary for ubiquitination of cyclin E (CCNE1 or CCNE2) and, subsequently, for normal G1 cell cycle progression. CUL4B regulates the mammalian target-of-rapamycin (mTOR) pathway, which controls cell growth, size, and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway depends on 26S proteasome function and requires interaction between CUL4B and MLST8. Along with CUL4A, CUL4B contributes to ribosome biogenesis.
CUL4B is also known as CUL-4B, MRXHF2, MRXS15, MRXSC, SFM2.
