Table 1.

Post-translational regulation of PHBs

Post-translational modification	Consequence	References
PHB1
Phosphorylation at Thr 258 by Akt	Inhibition of the interaction of PHB1 with PIP3 and Shp2 Localization of PHB1 in mitochondria to promote cell survival	[9] [12]
Phosphorylation at Thr 258 induced by PGE2 or growth factors such as EGF, HGF and IGF-1	Interaction of PHB1 with Ras, phospho-Akt(Ser 473), phospho-Raf-1(Ser 338), MEKK1 and IKKα/β(Ser 176/180) in the raft domain	[13]
Phosphorylation at Tyr 114 by the insulin receptor	Interaction with SH2 domain-containing tyrosine phosphatase-1 (Shp1) leading to a desensitization of insulin signaling	[14]
Phosphorylation of Tyr 249, Thr 258 and Tyr 259 by MEK1 and p38MAPK in response to FSH stimulation	Localization of PHB1 in mitochondria to promote cell survival and differentiation of ovarian granulosa cells	[15]
Phosphorylation at Tyr 114 and Tyr 259 by Lyn	Formation of a ternary complex consisting of PHB1, the IgE receptor FcεRI and the kinase Syk that triggers mast cell activation	[16]
Palmitoylation at its only cysteine residue (Cys 69)	Translocation of PHB1 to the plasma membrane Interaction with Eps 15 homology domain protein 2 (EHD2)	[16] [17]
Phosphorylation by PKC (possibly at Ser 8, Ser 129, Thr 155)	Localization of PHB1 in mitochondria to promote cell survival	[18]
Phosphorylation by both MEK1 and PKC-delta	Promotion of cell survival and invasion and inhibition of inner mitochondrial permeability	[18]
Phosphorylation at Ser 82 and Ser 218 by Aurora and/or Polo-Like Kinase	Regulation of mitosis	[19]
Conjugation to O-GlcNAc by O-GlcNAc transferase at Ser121 and Thr258 in response to hyperglycemia	Suppression of the phosphorylation at Tyr residues in the vicinity of this modification	[20]
Tyrosine nitrosylation	Associated with mitochondrial dysfunction	[21]
Ubiquitination by E3 ligase TRIM21	Degradation of PHB1. A tumor suppressor, LPLUNC1, stabilizes PHB1 by inhibiting its ubiquitination	[22]
Transamidation by Transglutaminase 2 (TG2) of Gln residues with some primary amines, including interacting proteins	Involvement in insulin secretion Cross-link with interacting mitochondrial proteins to promote neuroprotection	[23–25]
Oxidation at Cys69 by ROS upon alcohol exposure	Possible induction of mitochondrial dysfunction and cellular injury	[26]
Deimination of an Arg residue by peptidylarginine deiminases	Possible modulation of PHB1 function and involvement in cancer etiology	[27]
Ubiquitination by Skp2B	Degradation of PHB1 leading to a defect in the activity of p53	[28–30]
PHB2
Phosphorylation at Ser 105, Ser 151, Ser 243 and Ser 286 by Aurora and/or Polo-Like Kinase	Regulation of mitosis	[19]
Phosphorylation at Ser 91 and Ser 176 by Akt	Involvement in all-trans retinoic acid-induced differentiation of human acute promyelocytic leukemia cells	[31]
Phosphorylation at Ser 91 by CaMK IV	Repression of MEF2 transcriptional activity to inhibit muscle differentiation	[32]
Phosphorylation at Tyr 248, possibly by Akt, RSK, S6 or TnK1	Undetermined	[33]
Phosphorylation at Tyr 128	Associated with cancer (identified during phosphotyrosine profiling of cancer cell proteome)	[34]
Phosphorylation at Ser 39 by PKCα	Suppression of ERα signalling	[35]
Dephosphorylation at Ser 39 by PP1Cα complexed to guanine nucleotide-exchange protein 3 (BIG3)	Activation of ERα signalling	[35]